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ISSN: 2056-9890
Volume 71| Part 11| November 2015| Pages 1401-1407
https://doi.org/10.1107/S2056989015020046

Crystal structure and absolute configuration of (3S,4aS,8aS)-N-tert-butyl-2-[(S)-3-(2-chloro-4-nitro­benzamido)-2-hy­dr­oxy­prop­yl]deca­hydro­iso­quinoline-3-carboxamide and (3S,4aS,8aS)-N-tert-butyl-2-{(S)-2-[(S)-1-(2-chloro-4-nitro­benzoyl)pyrrolidin-2-yl]-2-hy­dr­oxy­eth­yl}deca­hydro­iso­quinoline-3-carboxamide

Tucker Maxson,a Jeffery A. Bertke,b* Danielle L. Grayb and Douglas A. Mitchella

aDepartment of Chemistry, University of Illinois, 345 Roger Adams Lab, 600 South Mathews Avenue, Urbana, IL 61801, USA, and bUniversity of Illinois, School of Chemical Sciences, Box 59-1, 505 South Mathews Avenue, Urbana, Illinois 61801, USA
*Correspondence e-mail: jbertke@illinois.edu

Edited by S. Parkin, University of Kentucky, USA (Received 10 October 2015; accepted 22 October 2015; online 31 October 2015)

The crystal structure and absolute configuration of the two new title nelfinavir analogs, C24H35ClN4O5, (I), and C27H39ClN4O5, (II), have been determined. Each of these mol­ecules exhibits a number of disordered moieties. There are intra­molecular N—H⋯O hydrogen bonds in both (I) and (II). In (I) it involves the two carboxamide groups, while in (II) it involves the N-tert-butyl carboxamide group and the 2-hydroxyl O atom. The inter­molecular hydrogen bonding in (I) (O—H⋯O and N—H⋯O) leads to two-dimensional sheets that extend parallel to the ac plane. The inter­molecular hydrogen bonding in (II) (O—H⋯O) leads to chains that extend parallel to the a axis.

CCDC references: 1432733; 1432732

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1. Chemical context

Nelfinavir (Viracept) is an FDA approved HIV protease inhibitor identified through structure-based design with a low nanomolar inhibitory concentration against the HIV aspartyl protease (Kaldor et al., 1997[Kaldor, S. W., Kalish, V. J., Davies, J. F., 2nd Shetty, B. V., Fritz, J. E., Appelt, K., Burgess, J. A., Campanale, K. M., Chirgadze, N. Y., Clawson, D. K., Dressman, B. A., Hatch, S. D., Khalil, D. A., Kosa, M. B., Lubbehusen, P. P., Muesing, M. A., Patick, A. K., Reich, S. H., Su, K. S. & Tatlock, J. H. (1997). J. Med. Chem. 40, 3979-3985.]). Although nelfinavir is no longer recommended as a first-line treatment against HIV due to its inferior efficacy compared to alternative protease inhibitors (Panel on Anti­retroviral Guidelines, 2015[Panel on Antiretroviral Guidelines (2015). Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.]), it has been found to have a number of additional biological activities that may have therapeutic utility, including anti­viral (against other human viruses) (Yamamoto et al., 2004[Yamamoto, N., Yang, R., Yoshinaka, Y., Amari, S., Nakano, T., Cinatl, J., Rabenau, H., Doerr, H. W., Hunsmann, G., Otaka, A., Tamamura, H., Fujii, N. & Yamamoto, N. (2004). Biochem. Biophys. Res. Commun. 318, 719-725.]; Kalu et al., 2014[Kalu, N. N., Desai, P. J., Shirley, C. M., Gibson, W., Dennis, P. A. & Ambinder, R. F. (2014). J. Virol. 88, 5455-5461.]), anti­cancer (Gantt et al., 2013[Gantt, S., Casper, C. & Ambinder, R. F. (2013). Curr. Opin. Oncol. 25, 495-502.]; Koltai, 2015[Koltai, T. (2015). F1000Res. 4, 1-19.]), and anti­virulence activity (Maxson et al., 2015[Maxson, T., Deane, C. D., Molloy, E. M., Cox, C. L., Markley, A. L., Lee, S. W. & Mitchell, D. A. (2015). ACS Chem. Biol. 10, 1217-1226.]). However, nelfinavir was originally designed with only the HIV protease active site in mind and the structure is likely not optimal for binding to the alternative targets involved in these other activities. We recently reported on the synthesis of a collection of nelfinavir analogs that may be of inter­est for efforts to repurpose the drug (Maxson et al., 2015[Maxson, T., Deane, C. D., Molloy, E. M., Cox, C. L., Markley, A. L., Lee, S. W. & Mitchell, D. A. (2015). ACS Chem. Biol. 10, 1217-1226.]).

The syntheses of the title compounds were achieved by a previously reported route that utilizes the configuration of the amino acid starting material to control the stereochemical outcome of the sodium borohydride reduction of the chloro­methyl ketone (Kaldor et al., 1997[Kaldor, S. W., Kalish, V. J., Davies, J. F., 2nd Shetty, B. V., Fritz, J. E., Appelt, K., Burgess, J. A., Campanale, K. M., Chirgadze, N. Y., Clawson, D. K., Dressman, B. A., Hatch, S. D., Khalil, D. A., Kosa, M. B., Lubbehusen, P. P., Muesing, M. A., Patick, A. K., Reich, S. H., Su, K. S. & Tatlock, J. H. (1997). J. Med. Chem. 40, 3979-3985.]). However, the reduction of compound (I)[link], derived from achiral glycine, results in a racemic mixture (Fig. 1[link]), while the reduction of compound (II)[link], derived from L-proline, does not benefit from a strong directing influence from the existing chiral center (Fig. 2[link]). The products of the two reductions were carried forward through the remainder of each synthesis to generate the title compounds. The absolute configurations of compounds (I)[link] and (II)[link], as well as the conformations they adopt due to the increased flexibility and rigidity, respectively, relative to nelfinavir was investigated by X-ray diffraction.

[Scheme 1]
[Figure 1]
Figure 1
The synthesis of (I)[link].
[Figure 2]
Figure 2
The synthesis of (II)[link].

2. Structural commentary

The core mol­ecular structures of (I)[link] and (II)[link] are comprised of N-tert-butyl-2-(2-hy­droxy­alk­yl)deca­hydro­iso­quinoline-3-carb­ox­amide groups. The difference between the two species comes from the substitution at the N position of the deca­hydro­iso­quinoline group. Compound (I)[link] has a (2-chloro-4-nitro­benzamido)-2-hy­droxy­propyl group at the N-atom position of the deca­hydro­iso­quinoline ring (Fig. 3[link]). Compound (II)[link] has a (2-chloro-4-nitro­benzo­yl)pyrrolidin-2-yl)-2-hy­droxy­ethyl group at the N-atom position (Fig. 4[link]).

[Figure 3]
Figure 3
Plot showing 35% probability ellipsoids for non-H atoms and circles of arbitrary size for H atoms for (I)[link]. Only the major component of disordered sites is shown.
[Figure 4]
Figure 4
Plot showing 35% probability ellipsoids for non-H atoms and circles of arbitrary size for H atoms for (II)[link]. Only the major component of disordered sites is shown.

There is disorder of the Cl group in (I)[link] over two positions with the site occupancies refining to 0.941 (8) and 0.059 (8) for Cl1 and Cl1B, respectively. The nitro group is disordered over two positions, with the site occupancies refining to 0.60 (2) and 0.40 (2). The NO2 group in one orientation is essentially coplanar with the phenyl ring [O1B—N1B—C4—C3; τ = 1(2)°] and in the other orientation is twisted slightly more out of plane [O1—N1—C4—C3; τ = −9.0 (13)°]. Both six-membered rings of the deca­hydro­iso­quinoline group in (I)[link] adopt a chair conformation, the dihedral angle between the best-fit planes of the cyclo­hexyl and piperidine moieties is 119.9 (15)°. There is one intra­molecular hydrogen-bonding inter­action in (I)[link] which involves the two carboxamide groups (N2—H2⋯O5; Table 1[link]). The Flack x parameter of −0.008 (18) and the Hooft y parameter of −0.010 (19) indicate that the absolute configuration of (I)[link] has been assigned correctly.

Table 1
Hydrogen-bond geometry (Å, °) for (I)[link]

D—H⋯A D—H H⋯A D⋯A D—H⋯A
O4—H4B⋯O5i 0.87 (4) 1.94 (4) 2.791 (2) 169 (3)
N2—H2⋯O5 0.83 (3) 2.11 (3) 2.928 (3) 169 (3)
N4—H4⋯O3ii 0.84 (3) 2.15 (3) 2.964 (2) 161 (3)
Symmetry codes: (i) x, y, z+1; (ii) [x+{\script{1\over 2}}, -y+{\script{3\over 2}}, -z+2].

There are multiple disordered moieties in (II)[link], the nitro group is disordered over two positions with the site occupancies for the two orientations refining to 0.967 (6) and 0.033 (8). In both orientations, the NO2 group is twisted out of the plane of the phenyl ring; the major orientation is twisted out of the plane less [O1—N1—C3—C2; τ = 10.9 (4)°] than the minor orientation [O1B—N1B—C3—C2; τ = −26 (6)°]. The carbonyl C7—O3 group is disordered over two positions, with the site occupancies refining to 0.58 (2) and 0.42 (2). In the minor orientation, the CO group is nearly normal to the plane of the phenyl ring [O3B—C7B—C6—C5; τ = −89 (3)°], while the major orientation is significantly less out of plane [O3—C7—C6—C5; τ = −44 (3)°]. The final two disordered moieties of (II)[link] are a portion of the pyrrolidin-2-yl group and the three methyl groups of tert-butyl. The C10 and C11 atoms of the pyrrolidin-2-yl group are disordered over two positions, with site occupancies of 0.669 (16) and 0.331 (16). The tert-butyl methyl groups are also disordered over two positions via a slight rotation around the N4—C24 bond, the site occupancies refining to 0.811 (17) and 0.189 (17). Similar to (I)[link], both six-membered rings of the deca­hydro­iso­quinoline group in (II)[link] adopt a chair conformation, with a dihedral angle between the best-fit planes of the cyclo­hexyl and piperidine moieties of 116.3 (17)°. There is one weak intra­molecular hydrogen-bonding inter­action in (II)[link], involving the N-tert-butyl carboxamide group and the 2-hydroxyl O atom (N4—H4C⋯O4; Table 2[link]). The Flack x parameter of 0.036 (19) and the Hooft y parameter of 0.03 (2) indicate that the absolute configuration of (II)[link] has been assigned correctly.

Table 2
Hydrogen-bond geometry (Å, °) for (II)[link]

D—H⋯A D—H H⋯A D⋯A D—H⋯A
N4—H4C⋯O4 0.88 (3) 2.60 (3) 3.219 (3) 129 (3)
O4—H4B⋯O5i 0.82 (1) 1.89 (2) 2.709 (2) 170 (4)
Symmetry code: (i) x-1, y, z.

3. Supra­molecular features

The extended structure of (I)[link] is a two-dimensional sheet of hydrogen-bonded mol­ecules extending in the ac plane (Fig. 5[link]a). Each mol­ecule of (I)[link] is hydrogen bonded to four neighboring mol­ecules via O—H⋯O and N—H⋯O inter­actions; the details of these inter­actions can be found in Table 1[link]. The two-dimensional layers stack in an ABAB pattern along the crystallographic b axis (Fig. 5[link]b). The layers are separated by the bulky deca­hydro­iso­quinoline groups, which protrude above and below the sheets. The layers alternate between these bulky groups pointing `left' and `right', this along with a slight offset between the A and B layers allows them to inter­digitate.

[Figure 5]
Figure 5
A plot of the packing of (I)[link] viewed (a) along the b axis, showing a hydrogen-bonded two-dimensional sheet overlaid with the unit cell, and (b) along the c axis, showing how two layers stack together along the b axis. Only the major component of disordered sites are shown. Red dashed lines indicate inter­molecular hydrogen bonding and blue dashed lines indicate intra­molecular hydrogen bonding.

The extended structure of (II)[link] is a one-dimensional chain of hydrogen-bonded mol­ecules extending parallel to the crystallographic a axis (Fig. 6[link]a). Each mol­ecule of (II)[link] is hydrogen bonded to two neighboring mol­ecules via O—H⋯O inter­actions, the details of these inter­actions can be found in Table 2[link]. The one-dimensional chains are separated by the bulky deca­hydro­iso­quinoline groups and the tert-butyl groups, which prevent the chains from linking via further hydrogen-bonding inter­actions (Fig. 6[link]b).

[Figure 6]
Figure 6
A plot of the packing of (II)[link] viewed (a) along the c axis, showing a hydrogen-bonded one-dimensional chain, and (b) along the a axis, showing how the one-dimensional chains pack together overlaid with the unit cell. Only the major component of disordered sites is shown. Red dashed lines indicate inter­molecular hydrogen bonding and blue dashed lines indicate intra­molecular hydrogen bonding.

4. Database survey

A search of the Cambridge Crystallographic Database (CSD; Groom & Allen, 2014[Groom, C. R. & Allen, F. H. (2014). Angew. Chem. Int. Ed. 53, 662-671.]) returns only three crystal structures with the N-(tert-but­yl)deca­hydro­iso­quinoline-3-carboxamide core. One of the structures is N-(tert-but­yl)deca­hydro­iso­quinoline-3-carboxamide (CSD refcode COVYAO; Zhao et al., 2006[Zhao, X. Y., Li, R. M., Ma, C. J. & Zhang, G. Y. (2006). J. East China Univ. Sci. Technol. 32, 1449-1453.]). The other two mol­ecules are nelfinavir derivatives like (I)[link] and (II)[link], which were isolated during optimization of the synthesis. The difference between these two mol­ecules comes via the substitution at the N-atom position of the deca­hydro­iso­quinoline group.

One compound has a 3-amino-2-hy­droxy-4-(phenyl­sulfan­yl)butyl group in this position (CSD refcode QONJUY; Inaba et al., 2000[Inaba, T., Yamada, Y., Abe, H., Sagawa, S. & Cho, H. (2000). J. Org. Chem. 65, 1623-1628.]) and the other has a 3-acet­oxy-2-(3-acet­oxy-2-methyl­benzoyl­amino)-4-(phenyl­sulfan­yl)butyl group at the N-atom position (CSD refcode GONKOJ; Inaba et al., 1998[Inaba, T., Birchler, A. G., Yamada, Y., Sagawa, S., Yokota, K., Ando, K. & Uchida, I. (1998). J. Org. Chem. 63, 7582-7583.]). Each of these mol­ecules has intra­molecular N—H⋯O hydrogen bonding. In QONJUY it involves the two carboxyamide groups similar to the situation in compound (I)[link]. In GONKOJ it involves the N-tert-butyl carboxamide group and the 2-hydroxyl O atom similar to the situation in compound (II)[link]. The core structure of each of these previously reported materials is similar to (I)[link] and (II)[link] in that both six-membered rings of the deca­hydro­iso­quinoline groups adopt chair conformations. The dihedral angle between the best-fit planes of the cyclo­hexyl and piperidine moieties for the 3-amino-2-hy­droxy-4-(phenyl­sulfan­yl)butyl-substituted mol­ecule is 117.1 (18)°. Similarly, this angle for the 3-acet­oxy-2-(3-acet­oxy-2-methyl­benzoyl­amino)-4-(phenyl­sulfan­yl)butyl-substituted mol­ecule is 116.8 (14)°.

5. Synthesis and crystallization

Compound (I)[link] was synthesized through the inter­mediate chloro­methyl hy­droxy 4 (Fig. 1[link]). Chloro­methyl ketone 3 (571 mg, 2.36 mmol) was dissolved in di­chloro­methane (7 ml) and methanol (4 ml) under nitro­gen. The reaction was cooled to 273 K and sodium borohydride (63 mg, 1.65 mmol) was added in one portion. The reaction was stirred cold for 1h before being quenched by the slow addition of 2 M HCl (2 ml). The reaction was dried and the solid was dissolved in ethyl acetate. The product was washed twice with water and once with brine, dried over sodium sulfate, and concentrated by rotary evaporation. The product was purified by silica flash column chromatography (gradient of 0–8% EtOAc in DCM) to yield racemic 4 as a colorless oil (yield 423 mg, 75% yield). 1H NMR (500 MHz, CDCl3): δ 7.33–7.28 (complex, 5H), 5.63 (t, J = 6 Hz, 1H), 5.06 (s, 2H), 3.88 (s, 2H), 3.48 (m, 2H), 3.39 (m, 1H), 3.22 (m, 1H). 13C NMR (500 MHz, CDCl3): δ 157.23, 135.93, 128.36, 128.06, 127.91, 70.52, 66.90, 46.44, 43.96. HRMS (m/z): [M + H]+ calculated for C11H15ClNO3, 244.0740; observed, 244.0741. For the synthesis of compound (I)[link], compound 5 (104 mg, 0.233 mmol) was dissolved in methanol (15 ml) with 10% palladium on carbon (74 mg, 0.070 mmol). The solution was degassed for 30 min before being placed under 1 atm of hydrogen and stirred for 2 h at room temperature. The reaction was filtered through celite, dried to a solid, and taken up in tetra­hydro­furan (5 ml). 2-Chloro-4-nitro­benzoic acid (52 mg, 0.256 mmol), 3-[3-(di­methyl­amino)­prop­yl]-1-ethyl­carbodi­imide hydro­chloride (49 mg, 0.256 mmol), and hy­droxy­benzotriazole hydrate (42 mg, 0.256 mmol) were added and the reaction was stirred at room temperature overnight. The reaction was taken up in ethyl acetate, washed once with sodium bicarbonate and once with brine, and dried over sodium sulfate. The product was purified by silica flash-column chromatography (gradient of 0–3% MeOH in DCM) to yield (I)[link] as a yellow solid (yield 77 mg, 67%). Crystals suitable for X-ray diffraction were obtained from the vapor diffusion of pentane into a solution of compound (I)[link] in ethyl acetate at room temperature. 1H NMR (500 MHz, CDCl3): δ 8.41 (q, J = 4 Hz, 1H), 8.24 (d, J = 2 Hz, 1H), 8.13 (dd, J1 = 2 Hz, J2 = 8.5 Hz, 1H), 7.76 (d, J = 8.5 Hz, 1H), 5.60 (s, 1H), 4.04 (m, 2H), 3.47 (dt, J1 = 4 Hz, J2 = 14 Hz, 1H), 3.35 (br, 1H), 2.71 (dd, J1 = 2 Hz, J2 = 11.5 Hz, 1H), 2.49 (dd, J1 = 3 Hz, J2 = 11.5 Hz, 1H), 2.36 (dd, J1 = 10 Hz, J2 = 12.5 Hz, 1H), 2.22 (dd, J1 = 5 Hz, J2 = 12.5 Hz, 1H), 2.18 (dd, J1 = 3 Hz, J2 = 11.5 Hz, 1H), 1.95 (q, J = 12 Hz, 1H), 1.80–1.08 (complex, 20H). 13C NMR (500 MHz, CDCl3): δ 174.16, 167.06, 148.39, 142.00, 132.80, 130.18, 124.96, 121.56, 70.40, 68.29, 59.09, 57.54, 51.27, 43.27, 35.83, 33.55, 31.02, 30.86, 28.39, 26.19, 25.52, 20.18. HRMS (m/z): [M + H]+ calculated for C24H36ClN4O5, 495.2374; observed, 495.2376.

Compound (II)[link] was synthesized through the inter­mediate chloro­methyl hydroxyl 7 (Fig. 2[link]). Chloro­methyl ketone 6 (860 mg, 3.05 mmol) was dissolved in di­chloro­methane (7 ml) and methanol (4 ml) under nitro­gen. The reaction was cooled to 273 K and sodium borohydride (81 mg, 2.14 mmol) was added in one portion. The reaction was stirred cold for 1h before being quenched by the slow addition of 2 M HCl (2 ml). The reaction was dried and the solid was dissolved in ethyl acetate. The product was washed twice with water and once with brine, dried over sodium sulfate, and concentrated by rotary evaporation. Thin-layer chromatography (TLC) analysis showed two diastereomers with the higher RF compound being the (S,R) product. Both diastereomers were purified by silica flash-column chromatography (gradient of 0–10% EtOAc in DCM) to yield the (S,S)-isomer as a white solid (yield 279 mg, 32%) and (S,R)-isomer (7) as a white solid (yield 429 mg, 50%). Characterization of the (S,R)-isomer (7): 1H NMR (500 MHz, CDCl3): δ 7.37–7.28 (complex, 5H), 5.13 (dd, J1 = 12.5 Hz, J2 = 16 Hz, 2H), 4.95 (d, J = 2 Hz, 1H), 4.11 (m, 1H), 3.81 (br s, 1H), 3.72 (d, J = 11 Hz, 1H), 3.55 (m, 2H), 3.37 (m, 1H), 2.03 (m, 1H), 1.89 (m, 1H), 1.81 (m, 1H), 1.72 (m, 1H). 13C NMR (500 MHz, CDCl3): δ 157.52, 136.04, 128.27, 127.87, 127.65, 74.69, 67.22, 60.57, 47.91, 47.05, 28.12, 23.94. HRMS (m/z): [M + H]+ calculated for C14H19ClNO3, 284.1053; observed, 284.1055. For the synthesis of compound (II)[link], compound 8 (218 mg, 0.620 mmol) was dissolved in tetra­hydro­furan (6 ml) with 2-chloro-4-nitro­benzoic acid (138 mg, 0.682 mmol), 3-[3-(di­methyl­amino)­prop­yl]-1-ethyl­carbodi­imide hydro­chloride (131 mg, 0.682 mmol), and hy­droxy­benzotriazole hydrate (111 mg, 0.682 mmol). The reaction was stirred at room temperature overnight. The reaction was taken up in ethyl acetate, washed once with sodium bicarbonate and once with brine, and dried over sodium sulfate. The product was purified by silica flash-column chromatography (gradient of 0–5% MeOH in DCM) to yield (II)[link] as a yellow solid (yield 248 mg, 72%). Crystals suitable for X-ray diffraction were obtained by layering pentane over a solution of compound (II)[link] in di­chloro­methane at room temperature. 1H NMR (500 MHz, CDCl3): δ 8.31 (d, J = 2 Hz, 1H), 8.20 (dd, J1 = 2 Hz, J2 = 8.5 Hz, 1H), 7.54 (d, J = 8.5 Hz, 1H), 6.87 (s, 1H), 5.31 (s, 1H), 4.36 (m, 1H), 3.99 (m, 1H), 3.24 (m, 2H), 2.91 (d, J = 11 Hz, 1H), 2.63 (m, 2H), 2.18–1.13 (complex, 26H). 13C NMR (500 MHz, CDCl3): δ 173.83, 172.95, 148.31, 142.45, 128.53, 124.96, 122.35, 121.69, 69.81, 69.73, 60.88, 58.37, 57.98, 50.55, 50.51, 49.05, 35.84, 33.23, 31.07, 30.80, 28.56, 28.20, 26.20, 25.46, 24.53, 20.16. HRMS (m/z): [M + H]+ calculated for C27H40N4O5Cl, 535.2687; observed, 535.2692.

6. Refinement

Crystal data, data collection and structure refinement details for (I)[link] and (II)[link] are summarized in Table 3[link]. Structural models consisting of the target mol­ecules were developed for (I)[link] and (II)[link]. Several disordered sites on each mol­ecule were modeled with disorder. In each case, like distances were restrained to be similar. Since the major and minor components of each disordered site are in such close proximity to each other, the displacement parameters were constrained to be equal. Methyl H atom positions, R—CH3, were optimized by rotation about R—C bonds with idealized C—H, R–H and H⋯H distances. All hy­droxy and amine H atoms were located in a difference Fourier map in good hydrogen-bonding environments (Hamilton & Ibers, 1968[Hamilton, W. C. & Ibers, J. A. (1968). In Hydrogen Bonding in Solids. New York: W. A. Benjamin Inc.]) and their distances were allowed to refine. The O4—H4B distance in (II)[link] was restrained to be 0.84 (2) Å. The remaining H atoms were included as riding idealized contributors. Methyl, hy­droxy and amine H atomU values were assigned as 1.5 times Ueq of the carrier atom; remaining H atom U values were assigned as 1.2 times the carrier atom Ueq. On the basis of 2237 unmerged Friedel opposites, the fractional contribution of the inverted twin component was negligible (Flack, 1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.]; Flack & Bernardinelli, 2000[Flack, H. D. & Bernardinelli, G. (2000). J. Appl. Cryst. 33, 1143-1148.]) for (I)[link]. The absolute structure parameter y was calculated using PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]). The resulting value was y = −0.010 (19), indicating that the absolute structure has been determined correctly (Hooft et al. 2008[Hooft, R. W. W., Straver, L. H. & Spek, A. L. (2008). J. Appl. Cryst. 41, 96-103.]). On the basis of 2720 unmerged Friedel opposites, the fractional contribution of the inverted twin component was negligible (Flack, 1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.]; Flack & Bernardinelli, 2000[Flack, H. D. & Bernardinelli, G. (2000). J. Appl. Cryst. 33, 1143-1148.]) for (II)[link]. The absolute structure parameter y was calculated using PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]). The resulting value was y = 0.03 (2) indicating that the absolute structure has been determined correctly (Hooft et al. 2008[Hooft, R. W. W., Straver, L. H. & Spek, A. L. (2008). J. Appl. Cryst. 41, 96-103.]).

Table 3
Experimental details

  (I) (II)
Crystal data
Chemical formula C24H35ClN4O5 C27H39ClN4O5
Mr 495.01 535.07
Crystal system, space group Orthorhombic, P21212 Monoclinic, P21
Temperature (K) 193 168
a, b, c (Å) 18.8408 (7), 20.2263 (8), 6.7923 (3) 6.4341 (7), 20.280 (2), 11.0377 (12)
α, β, γ (°) 90, 90, 90 90, 105.248 (1), 90
V (Å3) 2588.41 (18) 1389.5 (3)
Z 4 2
Radiation type Mo Kα Mo Kα
μ (mm−1) 0.19 0.18
Crystal size (mm) 0.37 × 0.36 × 0.29 0.86 × 0.65 × 0.15
 
Data collection
Diffractometer Siemens Platform/APEXII CCD Siemens Platform/APEXII CCD
Absorption correction Integration (SHELXTL/XPREP; Bruker, 2014[Bruker (2014). APEX2, SAINT, SHELXTL, XCIF, XPREP and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]) Integration (SHELXTL/XPREP; Bruker, 2014[Bruker (2014). APEX2, SAINT, SHELXTL, XCIF, XPREP and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.])
Tmin, Tmax 0.953, 0.960 0.892, 0.980
No. of measured, independent and observed [I > 2σ(I)] reflections 30342, 5243, 4694 16374, 5627, 5222
Rint 0.027 0.024
(sin θ/λ)max (Å−1) 0.623 0.625
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.035, 0.085, 1.03 0.032, 0.082, 1.04
No. of reflections 5243 5627
No. of parameters 333 377
No. of restraints 53 14
H-atom treatment H atoms treated by a mixture of independent and constrained refinement H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.34, −0.43 0.24, −0.21
Absolute structure Flack (1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.]); Hooft et al. (2008[Hooft, R. W. W., Straver, L. H. & Spek, A. L. (2008). J. Appl. Cryst. 41, 96-103.]); 2720 Friedels Flack (1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.]); Hooft et al. (2008[Hooft, R. W. W., Straver, L. H. & Spek, A. L. (2008). J. Appl. Cryst. 41, 96-103.]); 2720 Friedels
Absolute structure parameter −0.008 (18) 0.036 (19)
Computer programs: APEX2, SAINT, XPREP and XCIF (Bruker, 2014[Bruker (2014). APEX2, SAINT, SHELXTL, XCIF, XPREP and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXS2014 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), SHELXL2014 (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]), SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]), CrystalMaker (CrystalMaker, 1994[CrystalMaker (1994). CrystalMaker. CrystalMaker Software Ltd, Bicester, Oxfordshire, England. www.crystalmaker.com.]), and publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

Supporting information

CCDC references: 1432733; 1432732

Crystal structure: contains datablocks I, II. DOI: https://doi.org/10.1107/S2056989015020046/pk2566sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989015020046/pk2566Isup2.hkl

Structure factors: contains datablock II. DOI: https://doi.org/10.1107/S2056989015020046/pk2566IIsup3.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989015020046/pk2566Isup4.cdx

Supporting information file. DOI: https://doi.org/10.1107/S2056989015020046/pk2566IIsup5.cdx

checkCIF report


Computing details top

For both compounds, data collection: APEX2 (Bruker, 2014); cell refinement: SAINT (Bruker, 2014); data reduction: SAINT (Bruker, 2014), XPREP (Bruker, 2014), and SADABS (Bruker, 2014). Program(s) used to solve structure: SHELXS2014 (Sheldrick, 2008) for (I); SHELXS2014 (Sheldrick, 2015) for (II). For both compounds, program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015). Molecular graphics: SHELXTL (Sheldrick, 2008) and CrystalMaker (CrystalMaker, 1994) for (I); SHELXTL (Sheldrick, 2015) and CrystalMaker (CrystalMaker, 1994) for (II). For both compounds, software used to prepare material for publication: XCIF (Bruker, 2014) and publCIF (Westrip, 2010).

(I) (3S,4aS,8aS)-N-tert-Butyl-2-[(S)-3-(2-chloro-4-nitrobenzamido)-2-hydroxypropyl]decahydroisoquinoline-3-carboxamide top
Crystal data top
C24H35ClN4O5F(000) = 1056
Mr = 495.01Dx = 1.270 Mg m−3
Orthorhombic, P21212Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2 2abCell parameters from 9966 reflections
a = 18.8408 (7) Åθ = 2.3–24.5°
b = 20.2263 (8) ŵ = 0.19 mm−1
c = 6.7923 (3) ÅT = 193 K
V = 2588.41 (18) Å3Prism, colourless
Z = 40.37 × 0.36 × 0.29 mm
Data collection top
Siemens Platform/APEXII CCD
diffractometer		5243 independent reflections
Radiation source: normal-focus sealed tube4694 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.027
profile data from φ and ω scansθmax = 26.3°, θmin = 1.5°
Absorption correction: integration
(SHELXTL/XPREP; Bruker, 2014)		h = −23→23
Tmin = 0.953, Tmax = 0.960k = −25→25
30342 measured reflectionsl = −8→8
Refinement top
Refinement on F2Hydrogen site location: mixed
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.035 w = 1/[σ2(Fo2) + (0.0355P)2 + 0.5785P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.085(Δ/σ)max = 0.001
S = 1.03Δρmax = 0.34 e Å−3
5243 reflectionsΔρmin = −0.43 e Å−3
333 parametersAbsolute structure: Flack (1983); Hooft et al. (2008); 2720 Friedels
53 restraintsAbsolute structure parameter: −0.008 (18)
Special details top

Experimental. One distinct cell was identified using APEX2 (Bruker, 2014). Four frame series were integrated and filtered for statistical outliers using SAINT (Bruker, 2014) then corrected for absorption by integration using SHELXTL/XPREP V2005/2 (Bruker, 2014) before using SAINT/SADABS (Bruker, 2014) to sort, merge, and scale the combined data No decay correction was applied.

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Structure was phased by direct (Sheldrick, 2015). Systematic conditions suggested the ambiguous space group. The space group choice was confirmed by successful convergence of the full-matrix least-squares refinement on F2. The final map had no significant features. A final analysis of variance between observed and calculated structure factors showed no dependence on amplitude or resolution.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/UeqOcc. (<1)
Cl10.29551 (15)0.69804 (7)0.67519 (15)0.0735 (5)0.941 (8)
Cl1B0.326 (2)0.6888 (7)0.664 (3)0.0735 (5)0.059 (8)
O10.3558 (8)0.8988 (8)0.2519 (16)0.086 (2)0.60 (2)
O20.4046 (8)0.9713 (5)0.445 (2)0.116 (3)0.60 (2)
N10.3808 (6)0.9169 (5)0.4064 (12)0.0715 (17)0.60 (2)
O1B0.3725 (13)0.9134 (12)0.271 (3)0.086 (2)0.40 (2)
O2B0.4360 (11)0.9754 (7)0.453 (3)0.116 (3)0.40 (2)
N1B0.3991 (9)0.9260 (7)0.431 (2)0.0715 (17)0.40 (2)
C10.38040 (11)0.78173 (14)0.8790 (4)0.0477 (6)
C20.34335 (12)0.77084 (14)0.7057 (4)0.0520 (7)
C30.34488 (14)0.81498 (16)0.5532 (4)0.0585 (7)
H3A0.32070.80620.43330.070*
C40.38270 (16)0.87247 (16)0.5797 (5)0.0635 (8)
C50.41913 (17)0.88668 (15)0.7505 (5)0.0675 (8)
H5A0.44390.92720.76580.081*
C60.41831 (14)0.84036 (15)0.8974 (5)0.0594 (7)
H6A0.44430.84851.01480.071*
C70.38161 (12)0.73281 (14)1.0445 (4)0.0478 (6)
O30.32755 (9)0.71943 (11)1.1373 (3)0.0644 (5)
O40.48956 (9)0.73984 (10)1.4849 (3)0.0534 (5)
H4B0.5165 (17)0.7479 (17)1.585 (5)0.080*
O50.56221 (7)0.75831 (7)0.8387 (2)0.0372 (3)
N20.44567 (10)0.70759 (11)1.0807 (3)0.0438 (5)
H20.4786 (16)0.7171 (15)1.005 (5)0.066*
N30.60919 (9)0.66293 (9)1.1177 (3)0.0368 (4)
N40.67223 (10)0.80363 (9)0.8528 (3)0.0417 (4)
H40.7145 (16)0.7950 (14)0.884 (4)0.063*
C80.46111 (12)0.66114 (13)1.2385 (4)0.0459 (6)
H8A0.47660.61861.18050.055*
H8B0.41720.65281.31450.055*
C90.51828 (11)0.68604 (12)1.3772 (3)0.0420 (5)
H9A0.53100.64991.47120.050*
C100.58565 (11)0.70901 (12)1.2713 (3)0.0386 (5)
H10A0.57670.75281.21090.046*
H10B0.62420.71441.36910.046*
C110.65713 (11)0.69212 (11)0.9715 (3)0.0380 (5)
H11A0.70360.70261.03530.046*
C120.66899 (13)0.64166 (11)0.8056 (4)0.0410 (5)
H12A0.62300.63180.74130.049*
H12B0.70100.66100.70540.049*
C130.70138 (14)0.57736 (12)0.8829 (4)0.0494 (6)
H13A0.75000.58800.93260.059*
C140.70957 (16)0.52528 (13)0.7203 (4)0.0590 (7)
H14A0.73030.54670.60250.071*
H14B0.74340.49100.76560.071*
C150.64047 (16)0.49205 (14)0.6624 (4)0.0611 (7)
H15A0.65030.45650.56610.073*
H15B0.60890.52480.59880.073*
C160.60342 (19)0.46287 (13)0.8419 (5)0.0696 (9)
H16A0.63330.42760.89990.084*
H16B0.55760.44300.80190.084*
C170.59030 (17)0.51683 (13)0.9945 (4)0.0610 (8)
H17A0.55750.55020.93870.073*
H17B0.56710.49711.11150.073*
C180.65836 (16)0.55060 (13)1.0574 (4)0.0550 (7)
H18A0.68830.51651.12430.066*
C190.64454 (15)0.60538 (13)1.2068 (4)0.0505 (6)
H19A0.61450.58781.31430.061*
H19B0.69020.61961.26500.061*
C200.62618 (10)0.75493 (11)0.8828 (3)0.0354 (5)
C210.65543 (13)0.87079 (12)0.7767 (4)0.0480 (6)
C220.60827 (17)0.90585 (14)0.9239 (5)0.0679 (8)
H22A0.56440.88050.94220.102*
H22B0.59670.95010.87460.102*
H22C0.63320.90971.05000.102*
C230.62113 (16)0.86682 (14)0.5736 (5)0.0606 (8)
H23A0.57390.84680.58520.091*
H23B0.65070.83970.48660.091*
H23C0.61670.91140.51840.091*
C240.72639 (15)0.90696 (15)0.7599 (6)0.0682 (9)
H24A0.74960.90790.88900.102*
H24B0.71820.95230.71450.102*
H24C0.75690.88380.66550.102*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.0607 (12)0.1010 (6)0.0588 (5)−0.0165 (6)−0.0109 (5)−0.0190 (5)
Cl1B0.0607 (12)0.1010 (6)0.0588 (5)−0.0165 (6)−0.0109 (5)−0.0190 (5)
O10.088 (6)0.100 (6)0.068 (2)0.018 (4)−0.011 (3)0.008 (3)
O20.141 (8)0.076 (2)0.130 (3)−0.009 (4)−0.021 (6)0.021 (2)
N10.071 (4)0.068 (2)0.075 (3)0.023 (2)−0.011 (3)−0.005 (2)
O1B0.088 (6)0.100 (6)0.068 (2)0.018 (4)−0.011 (3)0.008 (3)
O2B0.141 (8)0.076 (2)0.130 (3)−0.009 (4)−0.021 (6)0.021 (2)
N1B0.071 (4)0.068 (2)0.075 (3)0.023 (2)−0.011 (3)−0.005 (2)
C10.0257 (10)0.0711 (16)0.0463 (14)0.0075 (10)−0.0005 (10)−0.0111 (13)
C20.0330 (12)0.0761 (18)0.0471 (14)0.0110 (12)−0.0037 (10)−0.0142 (14)
C30.0463 (15)0.0788 (19)0.0505 (15)0.0225 (14)−0.0057 (12)−0.0146 (15)
C40.0602 (17)0.0701 (19)0.0601 (18)0.0332 (15)0.0033 (15)−0.0002 (15)
C50.0662 (19)0.0567 (17)0.079 (2)0.0106 (14)−0.0035 (17)−0.0068 (16)
C60.0464 (14)0.0732 (19)0.0586 (17)0.0057 (14)−0.0091 (13)−0.0124 (15)
C70.0284 (11)0.0747 (17)0.0404 (13)−0.0032 (11)−0.0024 (10)−0.0109 (12)
O30.0297 (8)0.1063 (15)0.0571 (11)−0.0049 (9)0.0044 (8)0.0005 (12)
O40.0413 (9)0.0750 (13)0.0440 (9)0.0114 (9)−0.0038 (8)−0.0169 (9)
O50.0280 (7)0.0430 (8)0.0407 (8)−0.0008 (6)−0.0039 (6)0.0031 (7)
N20.0275 (9)0.0655 (14)0.0384 (10)−0.0050 (9)−0.0011 (8)−0.0050 (10)
N30.0375 (9)0.0411 (10)0.0318 (9)0.0061 (8)−0.0012 (8)0.0013 (8)
N40.0298 (9)0.0432 (10)0.0521 (12)−0.0032 (8)−0.0044 (9)0.0001 (10)
C80.0373 (12)0.0565 (14)0.0440 (13)−0.0060 (11)0.0017 (10)−0.0014 (12)
C90.0383 (12)0.0525 (13)0.0352 (11)0.0052 (10)−0.0004 (9)−0.0039 (11)
C100.0334 (11)0.0482 (13)0.0342 (11)0.0029 (9)−0.0056 (9)−0.0047 (10)
C110.0282 (10)0.0457 (12)0.0400 (12)0.0033 (9)−0.0032 (9)−0.0016 (10)
C120.0393 (12)0.0460 (12)0.0378 (12)0.0059 (10)0.0050 (10)0.0019 (10)
C130.0482 (13)0.0531 (14)0.0470 (14)0.0192 (12)0.0032 (12)0.0006 (12)
C140.0673 (17)0.0557 (16)0.0540 (16)0.0224 (14)0.0116 (14)0.0021 (13)
C150.0818 (19)0.0466 (14)0.0549 (16)0.0096 (13)0.0141 (15)−0.0024 (14)
C160.097 (2)0.0436 (14)0.069 (2)0.0034 (15)0.0223 (19)0.0010 (15)
C170.085 (2)0.0426 (14)0.0550 (16)0.0062 (14)0.0222 (15)0.0059 (12)
C180.0689 (17)0.0510 (14)0.0451 (14)0.0261 (14)0.0048 (13)0.0117 (12)
C190.0580 (15)0.0566 (15)0.0369 (13)0.0178 (12)−0.0022 (12)0.0067 (12)
C200.0301 (10)0.0414 (11)0.0348 (11)0.0002 (9)−0.0006 (9)−0.0043 (9)
C210.0411 (13)0.0378 (12)0.0653 (17)−0.0065 (10)−0.0019 (12)−0.0007 (12)
C220.0653 (18)0.0512 (15)0.087 (2)0.0017 (14)0.0045 (17)−0.0127 (16)
C230.0665 (18)0.0475 (14)0.0678 (19)−0.0086 (13)−0.0126 (15)0.0125 (14)
C240.0540 (16)0.0529 (16)0.098 (2)−0.0193 (13)−0.0009 (16)0.0024 (17)
Geometric parameters (Å, º) top
Cl1—C21.739 (3)C11—C201.522 (3)
Cl1B—C21.716 (12)C11—C121.536 (3)
O1—N11.207 (7)C11—H11A1.0000
O2—N11.217 (7)C12—C131.529 (3)
N1—C41.482 (7)C12—H12A0.9900
O1B—N1B1.226 (9)C12—H12B0.9900
O2B—N1B1.228 (10)C13—C141.534 (4)
N1B—C41.511 (9)C13—C181.535 (4)
C1—C21.386 (3)C13—H13A1.0000
C1—C61.390 (4)C14—C151.517 (4)
C1—C71.498 (4)C14—H14A0.9900
C2—C31.368 (4)C14—H14B0.9900
C3—C41.376 (5)C15—C161.524 (4)
C3—H3A0.9500C15—H15A0.9900
C4—C51.379 (5)C15—H15B0.9900
C5—C61.368 (4)C16—C171.525 (4)
C5—H5A0.9500C16—H16A0.9900
C6—H6A0.9500C16—H16B0.9900
C7—O31.228 (3)C17—C181.514 (4)
C7—N21.333 (3)C17—H17A0.9900
O4—C91.418 (3)C17—H17B0.9900
O4—H4B0.87 (4)C18—C191.525 (4)
O5—C201.244 (2)C18—H18A1.0000
N2—C81.455 (3)C19—H19A0.9900
N2—H20.83 (3)C19—H19B0.9900
N3—C111.467 (3)C21—C221.514 (4)
N3—C101.467 (3)C21—C231.526 (4)
N3—C191.471 (3)C21—C241.528 (3)
N4—C201.329 (3)C22—H22A0.9800
N4—C211.487 (3)C22—H22B0.9800
N4—H40.84 (3)C22—H22C0.9800
C8—C91.517 (3)C23—H23A0.9800
C8—H8A0.9900C23—H23B0.9800
C8—H8B0.9900C23—H23C0.9800
C9—C101.531 (3)C24—H24A0.9800
C9—H9A1.0000C24—H24B0.9800
C10—H10A0.9900C24—H24C0.9800
C10—H10B0.9900
O1—N1—O2127.3 (9)H12A—C12—H12B107.9
O1—N1—C4121.0 (9)C12—C13—C14112.2 (2)
O2—N1—C4111.6 (9)C12—C13—C18110.74 (19)
O1B—N1B—O2B120.6 (14)C14—C13—C18111.5 (2)
O1B—N1B—C4111.2 (14)C12—C13—H13A107.4
O2B—N1B—C4128.1 (14)C14—C13—H13A107.4
C2—C1—C6118.1 (3)C18—C13—H13A107.4
C2—C1—C7122.7 (2)C15—C14—C13113.9 (2)
C6—C1—C7119.2 (2)C15—C14—H14A108.8
C3—C2—C1121.9 (3)C13—C14—H14A108.8
C3—C2—Cl1B120.7 (7)C15—C14—H14B108.8
C1—C2—Cl1B113.0 (8)C13—C14—H14B108.8
C3—C2—Cl1118.2 (2)H14A—C14—H14B107.7
C1—C2—Cl1119.8 (2)C14—C15—C16110.9 (3)
C2—C3—C4117.6 (3)C14—C15—H15A109.5
C2—C3—H3A121.2C16—C15—H15A109.5
C4—C3—H3A121.2C14—C15—H15B109.5
C3—C4—C5123.0 (3)C16—C15—H15B109.5
C3—C4—N1113.4 (5)H15A—C15—H15B108.0
C5—C4—N1123.7 (5)C15—C16—C17109.9 (2)
C3—C4—N1B128.6 (7)C15—C16—H16A109.7
C5—C4—N1B108.1 (7)C17—C16—H16A109.7
C6—C5—C4117.7 (3)C15—C16—H16B109.7
C6—C5—H5A121.1C17—C16—H16B109.7
C4—C5—H5A121.1H16A—C16—H16B108.2
C5—C6—C1121.6 (3)C18—C17—C16112.2 (3)
C5—C6—H6A119.2C18—C17—H17A109.2
C1—C6—H6A119.2C16—C17—H17A109.2
O3—C7—N2124.9 (3)C18—C17—H17B109.2
O3—C7—C1121.2 (2)C16—C17—H17B109.2
N2—C7—C1113.9 (2)H17A—C17—H17B107.9
C9—O4—H4B109 (2)C17—C18—C19111.8 (2)
C7—N2—C8124.3 (2)C17—C18—C13112.8 (2)
C7—N2—H2118 (2)C19—C18—C13110.4 (2)
C8—N2—H2117 (2)C17—C18—H18A107.2
C11—N3—C10114.32 (17)C19—C18—H18A107.2
C11—N3—C19108.55 (18)C13—C18—H18A107.2
C10—N3—C19110.33 (18)N3—C19—C18112.3 (2)
C20—N4—C21126.27 (19)N3—C19—H19A109.2
C20—N4—H4115 (2)C18—C19—H19A109.2
C21—N4—H4119 (2)N3—C19—H19B109.2
N2—C8—C9112.7 (2)C18—C19—H19B109.2
N2—C8—H8A109.1H19A—C19—H19B107.9
C9—C8—H8A109.1O5—C20—N4123.7 (2)
N2—C8—H8B109.1O5—C20—C11120.82 (19)
C9—C8—H8B109.1N4—C20—C11115.44 (18)
H8A—C8—H8B107.8N4—C21—C22108.9 (2)
O4—C9—C8107.70 (19)N4—C21—C23110.9 (2)
O4—C9—C10109.00 (19)C22—C21—C23111.9 (2)
C8—C9—C10113.42 (19)N4—C21—C24106.1 (2)
O4—C9—H9A108.9C22—C21—C24109.8 (2)
C8—C9—H9A108.9C23—C21—C24109.2 (2)
C10—C9—H9A108.9C21—C22—H22A109.5
N3—C10—C9113.06 (18)C21—C22—H22B109.5
N3—C10—H10A109.0H22A—C22—H22B109.5
C9—C10—H10A109.0C21—C22—H22C109.5
N3—C10—H10B109.0H22A—C22—H22C109.5
C9—C10—H10B109.0H22B—C22—H22C109.5
H10A—C10—H10B107.8C21—C23—H23A109.5
N3—C11—C20111.60 (17)C21—C23—H23B109.5
N3—C11—C12108.59 (18)H23A—C23—H23B109.5
C20—C11—C12108.67 (18)C21—C23—H23C109.5
N3—C11—H11A109.3H23A—C23—H23C109.5
C20—C11—H11A109.3H23B—C23—H23C109.5
C12—C11—H11A109.3C21—C24—H24A109.5
C13—C12—C11111.81 (19)C21—C24—H24B109.5
C13—C12—H12A109.3H24A—C24—H24B109.5
C11—C12—H12A109.3C21—C24—H24C109.5
C13—C12—H12B109.3H24A—C24—H24C109.5
C11—C12—H12B109.3H24B—C24—H24C109.5
C6—C1—C2—C31.8 (4)C19—N3—C10—C9−77.0 (2)
C7—C1—C2—C3−177.6 (2)O4—C9—C10—N3−165.33 (18)
C6—C1—C2—Cl1B158.4 (14)C8—C9—C10—N3−45.4 (3)
C7—C1—C2—Cl1B−20.9 (14)C10—N3—C11—C20−52.4 (2)
C6—C1—C2—Cl1179.7 (2)C19—N3—C11—C20−176.07 (18)
C7—C1—C2—Cl10.3 (3)C10—N3—C11—C12−172.21 (17)
C1—C2—C3—C4−2.3 (4)C19—N3—C11—C1264.2 (2)
Cl1B—C2—C3—C4−157.2 (15)N3—C11—C12—C13−59.4 (2)
Cl1—C2—C3—C4179.8 (2)C20—C11—C12—C13178.98 (19)
C2—C3—C4—C50.7 (4)C11—C12—C13—C14176.8 (2)
C2—C3—C4—N1−179.8 (5)C11—C12—C13—C1851.5 (3)
C2—C3—C4—N1B173.4 (9)C12—C13—C14—C15−75.8 (3)
O1—N1—C4—C3−9.0 (13)C18—C13—C14—C1549.0 (3)
O2—N1—C4—C3168.9 (8)C13—C14—C15—C16−54.1 (3)
O1—N1—C4—C5170.5 (10)C14—C15—C16—C1757.2 (3)
O2—N1—C4—C5−11.6 (11)C15—C16—C17—C18−57.7 (3)
O1B—N1B—C4—C31 (2)C16—C17—C18—C19178.8 (2)
O2B—N1B—C4—C3−175.8 (15)C16—C17—C18—C1353.7 (3)
O1B—N1B—C4—C5174.8 (17)C12—C13—C18—C1777.4 (3)
O2B—N1B—C4—C5−2 (2)C14—C13—C18—C17−48.3 (3)
C3—C4—C5—C61.4 (4)C12—C13—C18—C19−48.5 (3)
N1—C4—C5—C6−178.1 (6)C14—C13—C18—C19−174.2 (2)
N1B—C4—C5—C6−172.6 (8)C11—N3—C19—C18−64.1 (3)
C4—C5—C6—C1−2.0 (4)C10—N3—C19—C18170.0 (2)
C2—C1—C6—C50.5 (4)C17—C18—C19—N3−70.8 (3)
C7—C1—C6—C5179.9 (2)C13—C18—C19—N355.7 (3)
C2—C1—C7—O3−65.7 (3)C21—N4—C20—O54.6 (4)
C6—C1—C7—O3115.0 (3)C21—N4—C20—C11−177.1 (2)
C2—C1—C7—N2115.6 (3)N3—C11—C20—O5−41.3 (3)
C6—C1—C7—N2−63.7 (3)C12—C11—C20—O578.4 (3)
O3—C7—N2—C8−1.1 (4)N3—C11—C20—N4140.4 (2)
C1—C7—N2—C8177.5 (2)C12—C11—C20—N4−99.9 (2)
C7—N2—C8—C9−122.8 (3)C20—N4—C21—C2264.5 (3)
N2—C8—C9—O469.4 (2)C20—N4—C21—C23−59.1 (3)
N2—C8—C9—C10−51.3 (3)C20—N4—C21—C24−177.5 (2)
C11—N3—C10—C9160.33 (18)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O4—H4B···O5i0.87 (4)1.94 (4)2.791 (2)169 (3)
N2—H2···O50.83 (3)2.11 (3)2.928 (3)169 (3)
N4—H4···O3ii0.84 (3)2.15 (3)2.964 (2)161 (3)
Symmetry codes: (i) x, y, z+1; (ii) x+1/2, −y+3/2, −z+2.
(II) (3S,4aS,8aS)-N-tert-Butyl-2-{(S)-2-[(S)-1-(2-chloro-4-nitrobenzoyl)pyrrolidin-2-yl]-2-hydroxyethyl}decahydroisoquinoline-3-carboxamide top
Crystal data top
C27H39ClN4O5F(000) = 572
Mr = 535.07Dx = 1.279 Mg m−3
Monoclinic, P21Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ybCell parameters from 7806 reflections
a = 6.4341 (7) Åθ = 2.8–26.3°
b = 20.280 (2) ŵ = 0.18 mm−1
c = 11.0377 (12) ÅT = 168 K
β = 105.248 (1)°Plates, colourless
V = 1389.5 (3) Å30.86 × 0.65 × 0.15 mm
Z = 2
Data collection top
Siemens Platform/APEXII CCD
diffractometer		5627 independent reflections
Radiation source: normal-focus sealed tube5222 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.024
profile data from φ and ω scansθmax = 26.4°, θmin = 1.9°
Absorption correction: integration
(SHELXTL/XPREP; Bruker, 2014)		h = −8→8
Tmin = 0.892, Tmax = 0.980k = −25→25
16374 measured reflectionsl = −13→13
Refinement top
Refinement on F2Hydrogen site location: mixed
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.032 w = 1/[σ2(Fo2) + (0.0447P)2 + 0.1276P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.082(Δ/σ)max < 0.001
S = 1.04Δρmax = 0.24 e Å−3
5627 reflectionsΔρmin = −0.21 e Å−3
377 parametersAbsolute structure: Flack (1983); Hooft et al. (2008); 2720 Friedels
14 restraintsAbsolute structure parameter: 0.036 (19)
Special details top

Experimental. One distinct cell was identified using APEX2 (Bruker, 2014). Four frame series were integrated and filtered for statistical outliers using SAINT (Bruker, 2014) then corrected for absorption by integration using SHELXTL/XPREP V2005/2 (Bruker, 2014) before using SAINT/SADABS (Bruker, 2014) to sort, merge, and scale the combined data. No decay correction was applied.

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Structure was phased by direct (Sheldrick, 2015) methods. Systematic conditions suggested the ambiguous space group. The space group choice was confirmed by successful convergence of the full-matrix least-squares refinement on F2. The final map had no significant features. A final analysis of variance between observed and calculated structure factors showed little dependence on amplitude and resolution.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/UeqOcc. (<1)
Cl10.18218 (12)0.27617 (3)0.58986 (6)0.05313 (19)
O10.7185 (5)0.41190 (18)0.9393 (3)0.0657 (8)0.967 (8)
O20.5309 (5)0.48339 (16)1.0083 (3)0.0796 (11)0.967 (8)
O1B0.658 (13)0.391 (2)0.970 (8)0.0657 (8)0.033 (8)
O2B0.605 (14)0.4966 (13)0.961 (9)0.0796 (11)0.033 (8)
N10.5493 (4)0.43973 (13)0.9347 (2)0.0521 (6)
O3−0.3816 (17)0.3687 (9)0.5659 (16)0.064 (2)0.58 (2)
C7−0.1974 (15)0.3696 (13)0.5438 (6)0.044 (3)0.58 (2)
O3B−0.341 (3)0.3487 (9)0.584 (2)0.064 (2)0.42 (2)
C7B−0.209 (2)0.3832 (18)0.5437 (8)0.044 (3)0.42 (2)
O4−0.0271 (3)0.50975 (9)0.45504 (16)0.0466 (4)
H4B−0.124 (4)0.5375 (14)0.441 (3)0.070*
O50.6776 (3)0.60681 (10)0.43924 (17)0.0497 (5)
N2−0.1962 (3)0.38062 (11)0.4242 (2)0.0434 (5)
N30.1541 (3)0.56188 (9)0.25105 (17)0.0349 (4)
N40.3515 (3)0.61688 (10)0.48165 (17)0.0354 (4)
H4C0.211 (5)0.6126 (16)0.452 (3)0.053*
C10.1816 (4)0.34965 (12)0.6715 (2)0.0407 (6)
C20.3653 (5)0.36560 (13)0.7648 (2)0.0419 (5)
H2A0.49180.33930.77940.050*
C30.3571 (4)0.42136 (13)0.8359 (2)0.0425 (6)
C40.1757 (5)0.46054 (15)0.8176 (3)0.0515 (7)
H4A0.17280.49770.86970.062*
C5−0.0004 (5)0.44390 (15)0.7217 (3)0.0505 (6)
H5A−0.12640.47030.70710.061*
C60.0008 (4)0.38941 (13)0.6450 (2)0.0417 (6)
C8−0.0147 (4)0.40027 (12)0.3737 (2)0.0355 (5)
H8A0.12540.38830.43420.043*
C9−0.0526 (4)0.35761 (14)0.2539 (3)0.0481 (6)
H9A−0.03480.38490.18290.058*
H9B0.05440.32140.26740.058*
C10−0.2747 (10)0.3296 (4)0.2237 (6)0.0504 (15)0.669 (16)
H10A−0.27190.28160.24010.060*0.669 (16)
H10B−0.35270.33790.13500.060*0.669 (16)
C11−0.3755 (11)0.3670 (4)0.3125 (7)0.0423 (15)0.669 (16)
H11A−0.44150.40860.27370.051*0.669 (16)
H11B−0.48780.34000.33530.051*0.669 (16)
C10B−0.2980 (17)0.3525 (8)0.2257 (15)0.0504 (15)0.331 (16)
H10C−0.36180.38980.17050.060*0.331 (16)
H10D−0.34390.31140.17770.060*0.331 (16)
C11B−0.392 (2)0.3527 (9)0.3383 (12)0.0423 (15)0.331 (16)
H11C−0.51910.38180.32680.051*0.331 (16)
H11D−0.42630.30790.36300.051*0.331 (16)
C12−0.0208 (4)0.47423 (12)0.3446 (2)0.0370 (5)
H12A−0.15220.48460.27570.044*
C130.1800 (4)0.49527 (12)0.3056 (2)0.0380 (5)
H13A0.30610.49450.37990.046*
H13B0.20730.46360.24330.046*
C140.3607 (3)0.59631 (12)0.2673 (2)0.0357 (5)
H14A0.45420.57060.22500.043*
C150.3232 (4)0.66580 (12)0.2091 (2)0.0369 (5)
H15A0.24240.69250.25640.044*
H15B0.46420.68740.21720.044*
C160.1982 (4)0.66434 (13)0.0704 (2)0.0380 (5)
H16A0.29010.64150.02300.046*
C170.1487 (4)0.73367 (15)0.0150 (2)0.0462 (6)
H17A0.28330.75980.03490.055*
H17B0.09680.7302−0.07760.055*
C18−0.0196 (4)0.76982 (15)0.0644 (2)0.0470 (6)
H18A0.03880.77860.15520.056*
H18B−0.05280.81270.02090.056*
C19−0.2244 (4)0.72936 (14)0.0435 (2)0.0451 (6)
H19A−0.29100.7249−0.04780.054*
H19B−0.32790.75270.08070.054*
C20−0.1805 (4)0.66089 (12)0.1020 (2)0.0381 (5)
H20A−0.31590.63510.08160.046*
H20B−0.13060.66520.19450.046*
C21−0.0090 (4)0.62377 (13)0.0539 (2)0.0374 (5)
H21A−0.06990.6159−0.03800.045*
C220.0428 (4)0.55715 (13)0.1167 (2)0.0396 (5)
H22A−0.09290.53220.10700.048*
H22B0.13440.53210.07360.048*
C230.4782 (3)0.60558 (11)0.4055 (2)0.0359 (5)
C240.4216 (4)0.62935 (12)0.6177 (2)0.0390 (5)
C250.2182 (7)0.6384 (4)0.6614 (5)0.0498 (13)0.811 (17)
H25A0.13000.59840.64300.075*0.811 (17)
H25B0.13610.67600.61730.075*0.811 (17)
H25C0.25730.64670.75210.075*0.811 (17)
C260.5534 (13)0.5704 (3)0.6839 (4)0.0572 (14)0.811 (17)
H26A0.46780.53000.66310.086*0.811 (17)
H26B0.59130.57730.77500.086*0.811 (17)
H26C0.68530.56620.65590.086*0.811 (17)
C270.5599 (11)0.6921 (3)0.6388 (7)0.0569 (15)0.811 (17)
H27A0.47870.72830.58940.085*0.811 (17)
H27B0.69180.68420.61240.085*0.811 (17)
H27C0.59770.70370.72810.085*0.811 (17)
C25B0.227 (4)0.6608 (14)0.651 (3)0.0498 (13)0.189 (17)
H25D0.09450.63900.60400.075*0.189 (17)
H25E0.22010.70780.62990.075*0.189 (17)
H25F0.24180.65580.74150.075*0.189 (17)
C26B0.461 (5)0.5602 (8)0.678 (2)0.0572 (14)0.189 (17)
H26D0.32580.53510.65690.086*0.189 (17)
H26E0.51220.56470.76970.086*0.189 (17)
H26F0.56920.53690.64650.086*0.189 (17)
C27B0.612 (4)0.6761 (14)0.659 (3)0.0569 (15)0.189 (17)
H27D0.74460.65340.65430.085*0.189 (17)
H27E0.62620.69030.74570.085*0.189 (17)
H27F0.58950.71480.60370.085*0.189 (17)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.0715 (4)0.0369 (3)0.0546 (4)−0.0005 (3)0.0230 (3)−0.0055 (3)
O10.0580 (14)0.0857 (18)0.0498 (14)0.0073 (14)0.0076 (10)−0.0005 (13)
O20.0664 (16)0.097 (2)0.0719 (18)−0.0101 (14)0.0123 (14)−0.0422 (16)
O1B0.0580 (14)0.0857 (18)0.0498 (14)0.0073 (14)0.0076 (10)−0.0005 (13)
O2B0.0664 (16)0.097 (2)0.0719 (18)−0.0101 (14)0.0123 (14)−0.0422 (16)
N10.0564 (14)0.0602 (15)0.0405 (12)−0.0036 (12)0.0143 (10)0.0005 (11)
O30.041 (4)0.092 (8)0.068 (4)−0.008 (3)0.029 (4)−0.011 (4)
C70.0435 (16)0.040 (10)0.0557 (16)−0.004 (3)0.0269 (13)−0.0166 (16)
O3B0.041 (4)0.092 (8)0.068 (4)−0.008 (3)0.029 (4)−0.011 (4)
C7B0.0435 (16)0.040 (10)0.0557 (16)−0.004 (3)0.0269 (13)−0.0166 (16)
O40.0528 (11)0.0454 (10)0.0399 (10)0.0172 (8)0.0090 (8)−0.0097 (8)
O50.0298 (8)0.0613 (12)0.0524 (11)0.0106 (8)0.0011 (7)−0.0171 (9)
N20.0344 (11)0.0495 (13)0.0480 (12)−0.0039 (9)0.0136 (9)−0.0135 (10)
N30.0322 (10)0.0374 (11)0.0333 (10)0.0008 (8)0.0054 (8)−0.0082 (8)
N40.0306 (9)0.0423 (11)0.0300 (10)0.0024 (8)0.0022 (7)−0.0053 (8)
C10.0582 (15)0.0342 (12)0.0379 (13)−0.0028 (11)0.0273 (12)−0.0015 (10)
C20.0528 (14)0.0417 (13)0.0363 (12)0.0041 (11)0.0208 (11)0.0064 (10)
C30.0525 (14)0.0448 (14)0.0336 (12)−0.0042 (11)0.0174 (10)0.0019 (10)
C40.0611 (17)0.0552 (16)0.0424 (15)0.0031 (13)0.0213 (13)−0.0126 (12)
C50.0487 (15)0.0599 (17)0.0469 (15)0.0071 (13)0.0196 (12)−0.0097 (13)
C60.0450 (14)0.0477 (14)0.0394 (13)−0.0040 (11)0.0233 (11)−0.0054 (11)
C80.0330 (11)0.0394 (12)0.0350 (12)0.0029 (9)0.0104 (9)−0.0048 (10)
C90.0539 (15)0.0443 (14)0.0461 (15)0.0056 (12)0.0131 (12)−0.0130 (12)
C100.073 (2)0.037 (4)0.0420 (16)−0.021 (3)0.0166 (17)−0.018 (3)
C110.0325 (16)0.035 (3)0.058 (3)−0.0071 (18)0.0089 (19)−0.004 (2)
C10B0.073 (2)0.037 (4)0.0420 (16)−0.021 (3)0.0166 (17)−0.018 (3)
C11B0.0325 (16)0.035 (3)0.058 (3)−0.0071 (18)0.0089 (19)−0.004 (2)
C120.0375 (12)0.0394 (12)0.0330 (11)0.0083 (10)0.0072 (9)−0.0068 (9)
C130.0360 (12)0.0345 (12)0.0410 (12)0.0050 (9)0.0059 (9)−0.0089 (10)
C140.0265 (10)0.0438 (13)0.0364 (12)0.0029 (9)0.0077 (9)−0.0106 (9)
C150.0291 (11)0.0472 (14)0.0357 (12)−0.0043 (10)0.0111 (9)−0.0062 (10)
C160.0304 (11)0.0535 (15)0.0325 (12)−0.0009 (10)0.0128 (9)−0.0049 (10)
C170.0409 (13)0.0614 (16)0.0383 (13)−0.0066 (12)0.0139 (10)0.0040 (12)
C180.0487 (14)0.0487 (14)0.0450 (14)−0.0002 (12)0.0148 (11)0.0057 (12)
C190.0378 (13)0.0583 (16)0.0398 (13)0.0056 (12)0.0111 (10)0.0010 (12)
C200.0272 (10)0.0520 (14)0.0355 (12)−0.0009 (10)0.0089 (9)−0.0009 (10)
C210.0322 (11)0.0523 (14)0.0267 (11)−0.0045 (10)0.0061 (8)−0.0095 (10)
C220.0365 (12)0.0462 (14)0.0346 (12)−0.0017 (10)0.0066 (9)−0.0137 (10)
C230.0315 (11)0.0353 (12)0.0387 (12)0.0057 (9)0.0052 (9)−0.0079 (10)
C240.0422 (13)0.0420 (13)0.0295 (11)0.0017 (10)0.0037 (9)−0.0019 (9)
C250.0545 (17)0.062 (4)0.0341 (18)−0.001 (2)0.0141 (12)−0.008 (3)
C260.054 (3)0.066 (2)0.0469 (18)0.007 (2)0.005 (2)0.0227 (17)
C270.072 (3)0.058 (3)0.039 (3)−0.015 (3)0.012 (2)−0.015 (2)
C25B0.0545 (17)0.062 (4)0.0341 (18)−0.001 (2)0.0141 (12)−0.008 (3)
C26B0.054 (3)0.066 (2)0.0469 (18)0.007 (2)0.005 (2)0.0227 (17)
C27B0.072 (3)0.058 (3)0.039 (3)−0.015 (3)0.012 (2)−0.015 (2)
Geometric parameters (Å, º) top
Cl1—C11.742 (2)C12—H12A1.0000
O1—N11.215 (3)C13—H13A0.9900
O2—N11.228 (3)C13—H13B0.9900
O1B—N11.210 (15)C14—C231.525 (3)
O2B—N11.219 (15)C14—C151.541 (3)
N1—C31.466 (3)C14—H14A1.0000
O3—C7B1.236 (18)C15—C161.531 (3)
O3—C71.271 (11)C15—H15A0.9900
C7—O3B1.20 (2)C15—H15B0.9900
C7—N21.341 (7)C16—C171.533 (4)
C7—C61.512 (7)C16—C211.536 (3)
O3B—C7B1.271 (14)C16—H16A1.0000
C7B—N21.343 (10)C17—C181.522 (4)
C7B—C61.513 (10)C17—H17A0.9900
O4—C121.425 (3)C17—H17B0.9900
O4—H4B0.824 (14)C18—C191.518 (4)
O5—C231.239 (3)C18—H18A0.9900
N2—C81.475 (3)C18—H18B0.9900
N2—C111.476 (5)C19—C201.526 (4)
N2—C11B1.477 (10)C19—H19A0.9900
N3—C221.470 (3)C19—H19B0.9900
N3—C141.470 (3)C20—C211.541 (3)
N3—C131.471 (3)C20—H20A0.9900
N4—C231.336 (3)C20—H20B0.9900
N4—C241.472 (3)C21—C221.515 (4)
N4—H4C0.88 (3)C21—H21A1.0000
C1—C61.382 (4)C22—H22A0.9900
C1—C21.387 (4)C22—H22B0.9900
C2—C31.385 (4)C24—C251.520 (4)
C2—H2A0.9500C24—C27B1.524 (13)
C3—C41.382 (4)C24—C271.535 (5)
C4—C51.374 (4)C24—C261.535 (4)
C4—H4A0.9500C24—C25B1.536 (13)
C5—C61.393 (4)C24—C26B1.545 (12)
C5—H5A0.9500C25—H25A0.9800
C8—C121.532 (3)C25—H25B0.9800
C8—C91.545 (3)C25—H25C0.9800
C8—H8A1.0000C26—H26A0.9800
C9—C101.492 (6)C26—H26B0.9800
C9—C10B1.531 (11)C26—H26C0.9800
C9—H9A0.9900C27—H27A0.9800
C9—H9B0.9900C27—H27B0.9800
C10—C111.514 (7)C27—H27C0.9800
C10—H10A0.9900C25B—H25D0.9800
C10—H10B0.9900C25B—H25E0.9800
C11—H11A0.9900C25B—H25F0.9800
C11—H11B0.9900C26B—H26D0.9800
C10B—C11B1.519 (11)C26B—H26E0.9800
C10B—H10C0.9900C26B—H26F0.9800
C10B—H10D0.9900C27B—H27D0.9800
C11B—H11C0.9900C27B—H27E0.9800
C11B—H11D0.9900C27B—H27F0.9800
C12—C131.526 (3)
O1B—N1—O2B126 (3)N3—C14—C23112.03 (19)
O1—N1—O2123.3 (3)N3—C14—C15110.24 (17)
O1B—N1—C3110 (3)C23—C14—C15106.64 (18)
O1—N1—C3119.0 (2)N3—C14—H14A109.3
O2B—N1—C3124 (3)C23—C14—H14A109.3
O2—N1—C3117.8 (3)C15—C14—H14A109.3
C7B—O3—C713 (3)C16—C15—C14112.51 (19)
O3B—C7—O322.9 (9)C16—C15—H15A109.1
O3B—C7—N2128.8 (12)C14—C15—H15A109.1
O3—C7—N2116.0 (12)C16—C15—H15B109.1
O3B—C7—C6113.6 (12)C14—C15—H15B109.1
O3—C7—C6120.7 (10)H15A—C15—H15B107.8
N2—C7—C6117.5 (7)C15—C16—C17112.4 (2)
C7—O3B—C7B13 (3)C15—C16—C21109.89 (19)
O3—C7B—O3B22.8 (9)C17—C16—C21111.2 (2)
O3—C7B—N2118.4 (11)C15—C16—H16A107.7
O3B—C7B—N2122.9 (19)C17—C16—H16A107.7
O3—C7B—C6123.1 (11)C21—C16—H16A107.7
O3B—C7B—C6109.5 (15)C18—C17—C16113.0 (2)
N2—C7B—C6117.2 (9)C18—C17—H17A109.0
C12—O4—H4B112 (2)C16—C17—H17A109.0
C7—N2—C7B12 (3)C18—C17—H17B109.0
C7—N2—C8128.8 (4)C16—C17—H17B109.0
C7B—N2—C8128.2 (5)H17A—C17—H17B107.8
C7—N2—C11125.8 (5)C19—C18—C17110.9 (2)
C8—N2—C11105.0 (4)C19—C18—H18A109.5
C7—N2—C11B110.1 (7)C17—C18—H18A109.5
C7B—N2—C11B112.6 (8)C19—C18—H18B109.5
C8—N2—C11B119.2 (6)C17—C18—H18B109.5
C22—N3—C14109.84 (18)H18A—C18—H18B108.1
C22—N3—C13109.01 (18)C18—C19—C20111.8 (2)
C14—N3—C13112.62 (18)C18—C19—H19A109.3
C23—N4—C24126.7 (2)C20—C19—H19A109.3
C23—N4—H4C118.8 (19)C18—C19—H19B109.3
C24—N4—H4C114.2 (19)C20—C19—H19B109.3
C6—C1—C2121.8 (2)H19A—C19—H19B107.9
C6—C1—Cl1120.4 (2)C19—C20—C21111.6 (2)
C2—C1—Cl1117.8 (2)C19—C20—H20A109.3
C3—C2—C1117.3 (2)C21—C20—H20A109.3
C3—C2—H2A121.3C19—C20—H20B109.3
C1—C2—H2A121.3C21—C20—H20B109.3
C4—C3—C2122.9 (2)H20A—C20—H20B108.0
C4—C3—N1118.5 (2)C22—C21—C16110.13 (19)
C2—C3—N1118.6 (2)C22—C21—C20111.7 (2)
C5—C4—C3117.7 (2)C16—C21—C20112.0 (2)
C5—C4—H4A121.2C22—C21—H21A107.6
C3—C4—H4A121.2C16—C21—H21A107.6
C4—C5—C6121.9 (3)C20—C21—H21A107.6
C4—C5—H5A119.1N3—C22—C21113.16 (18)
C6—C5—H5A119.1N3—C22—H22A108.9
C1—C6—C5118.2 (2)C21—C22—H22A108.9
C1—C6—C7120.0 (10)N3—C22—H22B108.9
C5—C6—C7121.4 (9)C21—C22—H22B108.9
C1—C6—C7B130.1 (13)H22A—C22—H22B107.8
C5—C6—C7B111.7 (13)O5—C23—N4124.3 (2)
C7—C6—C7B11 (2)O5—C23—C14120.3 (2)
N2—C8—C12111.36 (19)N4—C23—C14115.23 (18)
N2—C8—C9102.10 (19)N4—C24—C25106.6 (3)
C12—C8—C9112.3 (2)N4—C24—C27B114.8 (14)
N2—C8—H8A110.3N4—C24—C27107.9 (3)
C12—C8—H8A110.3C25—C24—C27111.4 (4)
C9—C8—H8A110.3N4—C24—C26109.6 (3)
C10—C9—C8109.3 (3)C25—C24—C26110.9 (3)
C10B—C9—C897.7 (6)C27—C24—C26110.3 (3)
C10—C9—H9A109.8N4—C24—C25B105.5 (12)
C8—C9—H9A109.8C27B—C24—C25B108.3 (18)
C10—C9—H9B109.8N4—C24—C26B104.9 (9)
C8—C9—H9B109.8C27B—C24—C26B114.1 (13)
H9A—C9—H9B108.3C25B—C24—C26B108.9 (13)
C9—C10—C11102.3 (6)C24—C25—H25A109.5
C9—C10—H10A111.3C24—C25—H25B109.5
C11—C10—H10A111.3H25A—C25—H25B109.5
C9—C10—H10B111.3C24—C25—H25C109.5
C11—C10—H10B111.3H25A—C25—H25C109.5
H10A—C10—H10B109.2H25B—C25—H25C109.5
N2—C11—C10105.1 (5)C24—C26—H26A109.5
N2—C11—H11A110.7C24—C26—H26B109.5
C10—C11—H11A110.7H26A—C26—H26B109.5
N2—C11—H11B110.7C24—C26—H26C109.5
C10—C11—H11B110.7H26A—C26—H26C109.5
H11A—C11—H11B108.8H26B—C26—H26C109.5
C11B—C10B—C9116.4 (11)C24—C27—H27A109.5
C11B—C10B—H10C108.2C24—C27—H27B109.5
C9—C10B—H10C108.2H27A—C27—H27B109.5
C11B—C10B—H10D108.2C24—C27—H27C109.5
C9—C10B—H10D108.2H27A—C27—H27C109.5
H10C—C10B—H10D107.3H27B—C27—H27C109.5
N2—C11B—C10B94.0 (9)C24—C25B—H25D109.5
N2—C11B—H11C112.9C24—C25B—H25E109.5
C10B—C11B—H11C112.9H25D—C25B—H25E109.5
N2—C11B—H11D112.9C24—C25B—H25F109.5
C10B—C11B—H11D112.9H25D—C25B—H25F109.5
H11C—C11B—H11D110.3H25E—C25B—H25F109.5
O4—C12—C13108.45 (19)C24—C26B—H26D109.5
O4—C12—C8108.7 (2)C24—C26B—H26E109.5
C13—C12—C8110.82 (18)H26D—C26B—H26E109.5
O4—C12—H12A109.6C24—C26B—H26F109.5
C13—C12—H12A109.6H26D—C26B—H26F109.5
C8—C12—H12A109.6H26E—C26B—H26F109.5
N3—C13—C12111.04 (18)C24—C27B—H27D109.5
N3—C13—H13A109.4C24—C27B—H27E109.5
C12—C13—H13A109.4H27D—C27B—H27E109.5
N3—C13—H13B109.4C24—C27B—H27F109.5
C12—C13—H13B109.4H27D—C27B—H27F109.5
H13A—C13—H13B108.0H27E—C27B—H27F109.5
C7B—O3—C7—O3B154 (6)O3B—C7B—C6—C5−89 (3)
C7B—O3—C7—N2−77 (3)N2—C7B—C6—C5125 (2)
C7B—O3—C7—C676 (3)O3—C7B—C6—C787 (5)
O3—C7—O3B—C7B−26 (5)O3B—C7B—C6—C767 (4)
N2—C7—O3B—C7B−88 (4)N2—C7B—C6—C7−80 (4)
C6—C7—O3B—C7B88 (3)C7—N2—C8—C12−100.6 (15)
C7—O3—C7B—O3B−25 (5)C7B—N2—C8—C12−85 (2)
C7—O3—C7B—N283 (4)C11—N2—C8—C1286.4 (4)
C7—O3—C7B—C6−84 (4)C11B—N2—C8—C1296.6 (9)
C7—O3B—C7B—O3153 (6)C7—N2—C8—C9139.3 (15)
C7—O3B—C7B—N268 (4)C7B—N2—C8—C9155 (2)
C7—O3B—C7B—C6−76 (3)C11—N2—C8—C9−33.6 (4)
O3B—C7—N2—C7B95 (4)C11B—N2—C8—C9−23.5 (9)
O3—C7—N2—C7B72 (4)N2—C8—C9—C1014.1 (5)
C6—C7—N2—C7B−81 (4)C12—C8—C9—C10−105.3 (4)
O3B—C7—N2—C8−174 (2)N2—C8—C9—C10B29.1 (7)
O3—C7—N2—C8163.8 (14)C12—C8—C9—C10B−90.3 (7)
C6—C7—N2—C811 (3)C8—C9—C10—C1110.2 (8)
O3—C7—N2—C11−25 (3)C7—N2—C11—C10−131.3 (15)
C6—C7—N2—C11−177.9 (10)C8—N2—C11—C1042.0 (7)
O3B—C7—N2—C11B−10 (4)C9—C10—C11—N2−31.3 (9)
O3—C7—N2—C11B−32 (3)C8—C9—C10B—C11B−31.8 (15)
C6—C7—N2—C11B174.6 (15)C7—N2—C11B—C10B−161.4 (15)
O3—C7B—N2—C7−87 (5)C7B—N2—C11B—C10B−174 (2)
O3B—C7B—N2—C7−61 (4)C8—N2—C11B—C10B4.3 (16)
C6—C7B—N2—C780 (4)C9—C10B—C11B—N218.3 (18)
O3—C7B—N2—C8174.9 (19)N2—C8—C12—O455.0 (2)
O3B—C7B—N2—C8−159.1 (18)C9—C8—C12—O4168.76 (19)
C6—C7B—N2—C8−18 (4)N2—C8—C12—C13174.05 (19)
O3—C7B—N2—C11B−7 (4)C9—C8—C12—C13−72.1 (2)
O3B—C7B—N2—C11B19 (4)C22—N3—C13—C12−85.1 (2)
C6—C7B—N2—C11B161 (2)C14—N3—C13—C12152.70 (18)
C6—C1—C2—C33.5 (3)O4—C12—C13—N3−73.4 (2)
Cl1—C1—C2—C3−174.92 (18)C8—C12—C13—N3167.38 (18)
C1—C2—C3—C40.3 (4)C22—N3—C14—C23177.20 (18)
C1—C2—C3—N1−179.6 (2)C13—N3—C14—C23−61.1 (2)
O1B—N1—C3—C4155 (6)C22—N3—C14—C1558.6 (2)
O1—N1—C3—C4−168.9 (3)C13—N3—C14—C15−179.68 (18)
O2B—N1—C3—C4−36 (7)N3—C14—C15—C16−56.0 (2)
O2—N1—C3—C410.2 (4)C23—C14—C15—C16−177.86 (18)
O1B—N1—C3—C2−26 (6)C14—C15—C16—C17176.37 (19)
O1—N1—C3—C210.9 (4)C14—C15—C16—C2152.0 (2)
O2B—N1—C3—C2144 (7)C15—C16—C17—C18−70.8 (3)
O2—N1—C3—C2−169.9 (3)C21—C16—C17—C1852.9 (3)
C2—C3—C4—C5−2.2 (4)C16—C17—C18—C19−55.0 (3)
N1—C3—C4—C5177.7 (2)C17—C18—C19—C2055.7 (3)
C3—C4—C5—C60.4 (4)C18—C19—C20—C21−55.3 (3)
C2—C1—C6—C5−5.2 (4)C15—C16—C21—C22−51.3 (2)
Cl1—C1—C6—C5173.2 (2)C17—C16—C21—C22−176.4 (2)
C2—C1—C6—C7−179.1 (6)C15—C16—C21—C2073.6 (2)
Cl1—C1—C6—C7−0.7 (6)C17—C16—C21—C20−51.5 (3)
C2—C1—C6—C7B176.1 (9)C19—C20—C21—C22177.21 (19)
Cl1—C1—C6—C7B−5.5 (10)C19—C20—C21—C1653.1 (3)
C4—C5—C6—C13.2 (4)C14—N3—C22—C21−61.1 (2)
C4—C5—C6—C7177.0 (7)C13—N3—C22—C21175.09 (19)
C4—C5—C6—C7B−177.9 (8)C16—C21—C22—N357.2 (2)
O3B—C7—C6—C1105 (2)C20—C21—C22—N3−67.9 (2)
O3—C7—C6—C1129 (2)C24—N4—C23—O5−3.2 (4)
N2—C7—C6—C1−79 (2)C24—N4—C23—C14−178.2 (2)
O3B—C7—C6—C5−69 (3)N3—C14—C23—O5149.4 (2)
O3—C7—C6—C5−44 (3)C15—C14—C23—O5−89.9 (2)
N2—C7—C6—C5107.5 (16)N3—C14—C23—N4−35.4 (3)
O3B—C7—C6—C7B−95 (4)C15—C14—C23—N485.3 (2)
O3—C7—C6—C7B−71 (4)C23—N4—C24—C25−179.4 (4)
N2—C7—C6—C7B81 (4)C23—N4—C24—C27B43.0 (15)
O3—C7B—C6—C1110 (3)C23—N4—C24—C2760.9 (4)
O3B—C7B—C6—C190 (2)C23—N4—C24—C26−59.3 (5)
N2—C7B—C6—C1−57 (3)C23—N4—C24—C25B162.1 (12)
O3—C7B—C6—C5−69 (3)C23—N4—C24—C26B−83.0 (13)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N4—H4C···O40.88 (3)2.60 (3)3.219 (3)129 (3)
O4—H4B···O5i0.82 (1)1.89 (2)2.709 (2)170 (4)
Symmetry code: (i) x−1, y, z.
 

Acknowledgements

This research was supported in part by the NIH Director's New Innovator Award Program (grant No. DP2 OD008463). TM was supported in part by fellowships from the Department of Chemistry at the University of Illinois at Urbana–Champaign and the NIH Chemical Biology Inter­face Training Program (T32 GM070421).

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ISSN: 2056-9890
Volume 71| Part 11| November 2015| Pages 1401-1407
https://doi.org/10.1107/S2056989015020046
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