research communications\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 80| Part 11| November 2024| Pages 1146-1150
https://doi.org/10.1107/S2056989024009794

Crystal structures of two different multi-component crystals consisting of 1-(3,4-di­meth­­oxy­benz­yl)-6,7-di­meth­­oxy­iso­quinoline and fumaric acid

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Hiroki Shibata,a,b* Aya Sakon,c Noriyuki Takatad and Hiroshi Takiyamab

aPharmaceutical Technology Division, Analytical Development Department, Chugai Pharmaceutical Co. Ltd., 5-5-1 Ukima, Kita-ku, Tokyo 115-8543, Japan, bDepartment of Applied Physics and Chemical Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan, cPharmaceutical Technology Division, Formulation Development Department, Chugai Pharmaceutical Co. Ltd., 216 Totsuka-cho, Totsuka-ku, Yokohama, Kanagawa 244-8602, Japan, and dManufacturing Technology Division, Quality Development Department, Chugai Pharma Manufacturing Co. Ltd., 2500 Takayanagi, Fujieda, Shizuoka 426-0041, Japan
*Correspondence e-mail: shibata.hiroki63@chugai-pharm.co.jp

Edited by Y. Ozawa, University of Hyogo, Japan (Received 13 August 2024; accepted 7 October 2024; online 11 October 2024)

Two different multi-component crystals consisting of papaverine [1-(3,4-di­meth­oxy­benz­yl)-6,7-di­meth­oxy­iso­quinoline, C20H21NO4] and fumaric acid [C4H4O4] were obtained. Single-crystal X-ray structure analysis revealed that one, C20H21NO4·1.5C4H4O4 (I), is a salt co-crystal composed of salt-forming and non-salt-forming mol­ecules, and the other, C20H21NO4·0.5C4H4O4 (II), is a salt–co-crystal inter­mediate (i.e., in an inter­mediate state between a salt and a co-crystal). In this study, one state (crystal structure at 100 K) within the salt–co-crystal continuum is defined as the ‘inter­mediate’.

CCDC references: 2312143; 2312144

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1. Chemical context

Papaverine (1-[3,4-di­meth­oxy­benz­yl]-6,7-di­meth­oxy­iso­quino­line) is an iso­quinoline alkaloid compound extracted from the mature seed capsules of poppies (Kang et al., 2018[Kang, D., Qiang, G., Du, L. & Du, G. (2018). Papaverine. In Natural Small Molecule Drugs from Plants. Springer, Singapore.]). It is an anti­spasmodic and vasodilator, used primarily in the treatment of smooth muscle spasms and for vasodilation and improvement of symptoms in acute arterial embolism, acute pulmonary embolism, peripheral circulatory disturbance, and coronary circulatory disturbance. The active pharmaceutical ingredient papaverine has been developed as a hydro­chloride salt whose crystal structure has been determined (Reynolds et al., 1974[Reynolds, C. D., Palmer, R. A. & Gorinsky, B. (1974). J. Cryst. Mol. Struct. 4, 213-225.]). In the pharmaceutical industry, studies on salt crystallization and co-crystallization are conducted for purposes such as improving the solid-state stability of the active pharmaceutical ingredient or improvement of its dissolution properties. Fumaric acid is a di­carb­oxy­lic acid and a cis–trans isomer of maleic acid and is used in the pharmaceutical industry as a counter-ion in salts and as a conformer of co-crystals. For example, among 1372 new drugs approved by the US Food and Drug Administration between 1939 and 2020, fumaric acid was used as a counter-ion in the salts of ten drugs (Bharate et al., 2021[Bharate, S. S. (2021). Pharm. Res. 38, 1307-1326.]). The recently developed COVID-19 anti­viral drug substance Ensitrelvir is crystallized as a co-crystal with fumaric acid (Kawajiri et al., 2023[Kawajiri, T., Kijima, A., Iimuro, A., Ohashi, E., Yamakawa, K., Agura, K., Masuda, K., Kouki, K., Kasamatsu, K., Yanagisawa, S., Nakashima, S., Shibahara, S., Toyota, T., Higuchi, T., Suto, T., Oohara, T., Maki, T., Sahara, N., Fukui, N., Wakamori, H., Ikemoto, H., Murakami, H., Ando, H., Hosoya, M., Sato, M., Suzuki, Y., Nakagawa, Y., Unoh, Y., Hirano, Y., Nagasawa, Y., Goda, S., Ohara, T. & Tsuritani, T. (2023). ACS Cent. Sci. 9, 836-843]).

In this work, we synthesized two multicomponent crystals — a salt co-crystal (I)[link] and a salt–co-crystal inter­mediate (II)[link] — consisting of papaverine 1 and fumaric acid 2, and we determined their crystal structures. In this study, one state (crystal structure at 100 K) within the salt–co-crystal continuum is defined as the ‘inter­mediate’.

[Scheme 1]

2. Structural commentary

The crystal structure of (I)[link] is shown in Fig. 1[link]. It crystallized with a 1:1.5 papaverine:fumaric acid stoichiometric ratio in the space group P[\overline{1}] with Z = 2, with one full mol­ecule of papaverine and three half mol­ecules of fumaric acid (fumaric acids A, B, and C) in the asymmetric unit. The three fumaric acid mol­ecules were positioned on a center of symmetry, with mol­ecules A and C being disordered over two positions (O39/O40/C41 and C33).

[Figure 1]
Figure 1
The mol­ecular structure of (I)[link]. Hydrogen bonds are shown as dashed lines and displacement ellipsoids are drawn at the 50% probability level. [Symmetry codes: (i) −x + 2, −y + 2, −z + 1; (ii) −x + 1, −y + 2, −z; (iii) −x + 2, −y + 2, −z + 2.]

Since the C30—O31 and C30—O32 distances of fumaric acid mol­ecule A are 1.248 (2) Å and 1.246 (3) Å, respectively, the carb­oxy group of mol­ecule A is dissociated (Childs et al., 2007[Childs, S. L., Stahly, P. & Park, A. (2007). Mol. Pharm. 4, 3, 323-338.]; Chen et al., 2012[Chen, J.-M., Wang, Z.-Z., Wu, C.-B., Li, S. & Lu, T.-B. (2012). CrystEngComm, 14, 6221-6229.]). In addition, N1 of the papaverine mol­ecule is protonated and is engaged in N—H⋯O hydrogen bonding (Table 1[link]). Therefore, it was determined that fumaric acid mol­ecule A and the papaverine mol­ecule form a salt. The fumaric acid mol­ecules B and C are hydrogen-bonded to fumaric acid mol­ecule A. The C34—O35 and C34—O36 distances in fumaric acid mol­ecule B are 1.324 (3) Å and 1.211 (2) Å, respectively, thus the carb­oxy group of mol­ecule B is not dissociated. The C38—O39A and C38—O40A distances in fumaric acid mol­ecule C are 1.280 (5) Å and 1.231 (6) Å, respectively, thus the carb­oxy group of mol­ecule C is not dissociated (Childs et al., 2007[Childs, S. L., Stahly, P. & Park, A. (2007). Mol. Pharm. 4, 3, 323-338.]; Chen et al., 2012[Chen, J.-M., Wang, Z.-Z., Wu, C.-B., Li, S. & Lu, T.-B. (2012). CrystEngComm, 14, 6221-6229.]). Therefore, this multicomponent crystal includes both salt-forming and non–salt-forming mol­ecules and was thus concluded to be a salt co-crystal, (I)[link].

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

D—H⋯A D—H H⋯A D⋯A D—H⋯A
N1—H1⋯O31 0.88 2.20 3.034 (3) 159
N1—H1⋯O32 0.88 2.18 2.919 (2) 141
O35—H35⋯O31 0.84 1.83 2.617 (2) 156
O39A—H39A⋯O32 0.84 1.67 2.502 (4) 169

The crystal structure of (II)[link] is given in Fig. 2[link]. It crystallized with a 1:0.5 papaverine:fumaric acid stoichiometric ratio in space group P21/n with Z = 4, with one full mol­ecule of papaverine and half a mol­ecule of fumaric acid in the asymmetric unit. The fumaric acid mol­ecule is positioned on the center of symmetry. The C30–O31 and C30–O32 distances in the fumaric acid mol­ecule are 1.306 (1) and 1.223 (1) Å, respectively, indicating that the carb­oxy­lic acid of the fumaric acid mol­ecule is not dissociated (Childs et al., 2007[Childs, S. L., Stahly, P. & Park, A. (2007). Mol. Pharm. 4, 3, 323-338.]; Chen et al., 2012[Chen, J.-M., Wang, Z.-Z., Wu, C.-B., Li, S. & Lu, T.-B. (2012). CrystEngComm, 14, 6221-6229.]). Therefore, the fumaric acid and papaverine mol­ecules were determined to form a co-crystal. However, the O—H⋯N hydrogen bond [D⋯A = 2.5687 (12) Å, Table 2[link]) is shorter than that in neutral or ionic synthons, which indicates an inter­mediate state between a salt and a co-crystal (Childs et al., 2007[Childs, S. L., Stahly, P. & Park, A. (2007). Mol. Pharm. 4, 3, 323-338.]; Thipparaboina et al., 2015[Thipparaboina, R., Kumar, D., Mittapalli, S., Balasubramanian, S., Nangia, A. & Shastri, N. R. (2015). Cryst. Growth Des. 15, 12, 5816-5826.]; Stevens et al., 2020[Stevens, J. S., Coultas, S., Jaye, C., Fischer, D. A. & Schroeder, S. L. M. (2020). Phys. Chem. Chem. Phys. 22, 4916-4923.]; Tothadi et al., 2021[Tothadi, S., Shaikh, T. R., Gupta, S., Dandela, R., Vinod, C. P. & Nangia, A. K. (2021). Cryst. Growth Des. 21, 2, 735-747.]; Kotte et al., 2023[Kotte, L., Pendota, V., Sreedhar, B. & Nanubolu, J. B. (2023). CrystEngComm, 25, 2662-2678.]). It was thus concluded that this multicomponent crystal, (II)[link], is a salt–co-crystal inter­mediate.

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

D—H⋯A D—H H⋯A D⋯A D—H⋯A
O31—H31⋯N1 0.84 (1) 1.73 (1) 2.5687 (12) 175 (1)
C9—H9⋯O32i 0.95 (1) 2.27 (1) 3.2191 (14) 176 (1)
Symmetry code: (i) [-x+1, -y+2, -z+1].
[Figure 2]
Figure 2
The mol­ecular structure of (II)[link]. The hydrogen bond is shown as a dashed line and displacement ellipsoids are drawn at the 50% probability level. [Symmetry code: (i) −x, −y + 1, −z + 1.]

3. Supra­molecular features

The combination of the same two components – papaverine and fumaric acid – led to two different multicomponent crystals each with a different stoichiometric ratio and packing. The fumaric acid mol­ecules in (I)[link] form a systematic two-dimensional sheet structure parallel to the ac plane with hydrogen bonds linking fumaric acid mol­ecules A, B, and C (Fig. 3[link]). The space between the fumaric acid sheets is filled with a two-dimensional layer of papaverine mol­ecules hydrogen-bonded to fumaric acid mol­ecules A, resulting in (I)[link] having a layered structure (Fig. 4[link]).

[Figure 3]
Figure 3
Systematic two-dimensional sheet structure of fumaric acid in (I)[link] viewed along the ac plane. Inter­molecular O—H⋯O hydrogen bonds are shown as dashed lines. One of the two disorder components has been omitted for clarity.
[Figure 4]
Figure 4
The layered structure of (I)[link] viewed along the a axis. Inter­molecular O—H⋯O and N—H⋯O hydrogen bonds are shown as dashed lines. All hydrogen atoms and one of the two disordered components of the fumaric acid mol­ecules have been omitted for clarity.

Compound (II)[link] exhibits a three-mol­ecule unit structure with hydrogen bonds between two papaverine mol­ecules and one fumaric acid mol­ecule (Fig. 5[link]). The H9⋯O32 and C9⋯O32 distances between two of these three-mol­ecule units are 2.2706 (14) and 3.2191 (14) Å, respectively, with a C9—H9⋯O32 angle of 176.13 (11)° (Fig. 6[link]a, Table 2[link]); thus, it was concluded that there is a C—H⋯O hydrogen bond (Steiner, 1997[Steiner, T. (1997). Chem. Commun. pp. 727-734.]). A ring structure consisting of two O—H⋯N hydrogen bonds and two C—H⋯O hydrogen bonds between two papaverine mol­ecules and two fumaric acid mol­ecules is observed (Fig. 6[link]a). As a result, a one-dimensional ribbon structure is formed by the combination of O—H⋯N and C—H⋯O hydrogen bonds (Fig. 6[link]b). The final crystal structure is formed by the repeated overlapping of these ribbon structures (Fig. 7[link]).

[Figure 5]
Figure 5
Structural unit in the crystal of (II)[link]. Inter­molecular O—H⋯N hydrogen bonds are shown as dashed lines.
[Figure 6]
Figure 6
One-dimensional ribbon structure of (II)[link]. Inter­molecular O—H⋯N and C—H⋯O hydrogen bonds are shown as dashed lines. (a) Enlarged view of hydrogen-bonded ring. (b) Overview of the one-dimensional ribbon structure.
[Figure 7]
Figure 7
The packing of (II)[link]. Each blue and green line represents a one-dimensional ribbon structure. All hydrogen atoms have been removed for clarity.

4. Database survey

A survey of the Cambridge Structural Database (WebCSD, v5.44, April 2023; Groom et al., 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]) for structures with papaverine resulted in four hits. Two crystal structures were free-base, single-component crystals [refcodes MVERIQ (Baggio & Baggio, 1973[Baggio, R. F. & Baggio, S. (1973). Cryst. Struct. Commun. 2, 251-253.]) and MVERIQ01 (Marek et al., 1997[Marek, J., Dostal, J. & Slavik, J. (1997). Z. Kristallogr. Cryst. Mater. 211, 649-650.])]. The other two crystals were salts: one was a hydro­chloride salt (refcode PAPAVC; Reynolds et al., 1974[Reynolds, C. D., Palmer, R. A. & Gorinsky, B. (1974). J. Cryst. Mol. Struct. 4, 213-225.]) and the other was a hydro­bromide salt (refcode ZZZGYK; Van Hulle et al., 1953[Van Hulle, A., Amelinckx, S. & Dekeyser, W. (1953). Acta Cryst. 6, 664-665.]). There were no reports of multi-component crystals of papaverine.

5. Synthesis and crystallization

Compound (I)[link] was prepared as follows. About 3 mg (0.009 mmol) of papaverine and 2 mg (0.018 mmol) of fumaric acid were dissolved in 0.025 mL of ethanol. The prepared solution was shaken at room temperature at 100 r.p.m. overnight, and clear light colorless, block-shaped crystals were obtained. Compound (II)[link] was prepared as follows. About 20 mg (0.06 mmol) of papaverine and 10 mg (0.09 mmol) of fumaric acid were dissolved in 0.28 mL of a mixture of acetone and water (6:1) with heating at 368K. The prepared solution was shaken at room temperature at 100 r.p.m. overnight, and clear, light, colorless, block-shaped crystals was obtained.

6. Refinement

Crystal data, data collection, and structure refinement details are summarized in Table 3[link]. The N-bound H atom in (I)[link] was positioned geometrically and refined using a riding model with isotropic displacement parameter Uiso(H) = 1.2Ueq(N). The O-bound H atoms in (I)[link] were located in difference-Fourier maps and refined with O—H = 0.84 Å and with isotropic displacement parameters Uiso(H) = 1.5Ueq(O). The C-bound H atoms in (I)[link] were positioned geometrically (C—H = 0.95, 0.98, and 0.99 Å for sp2-hybridized, methyl, and methyl­ene hydrogen atoms, respectively) and refined using a riding model, with isotropic displacement parameters Uiso(H) = 1.5Ueq(C) for methyl and Uiso(H) = 1.2Ueq(C) for all other H atoms. The fumaric acid was disordered over two positions (O39/O40/C41 and C33), for which occupancies were refined, converging to 0.598/0.402 and 0.742/0.258, respectively. Restraints by DFIX were applied for C38/O39/O40, O39/O40, O40/H40, O32/H40, and C38/H40. For compound (II)[link], there were no N-bound H atoms or disorders, and the refinement conditions for O-bound H atoms and C-bound H atoms were the same as those for compound (I)[link].

Table 3
Experimental details

  (I) (II)
Crystal data
Chemical formula C20H22NO4·1.5C4H4O4 C20H21NO4·0.5C4H4O4
Mr 513.48 397.43
Crystal system, space group Triclinic, P[\overline{1}] Monoclinic, P21/n
Temperature (K) 100 100
a, b, c (Å) 9.5290 (2), 10.5445 (3), 12.6509 (4) 9.05718 (12), 6.71363 (11), 32.8419 (4)
α, β, γ (°) 91.606 (2), 104.980 (2), 97.823 (2) 90, 95.9308 (12), 90
V (Å3) 1213.87 (6) 1986.31 (5)
Z 2 4
Radiation type Cu Kα Cu Kα
μ (mm−1) 0.92 0.80
Crystal size (mm) 0.17 × 0.08 × 0.03 0.22 × 0.11 × 0.11
 
Data collection
Diffractometer XtaLAB Synergy, Single source at home/near, HyPix3000 XtaLAB Synergy, Single source at home/near, HyPix3000
Absorption correction Multi-scan (CrysAlis PRO; Rigaku OD, 2022[Rigaku OD (2022). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]) Multi-scan (CrysAlis PRO; Rigaku OD, 2022[Rigaku OD (2022). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.])
Tmin, Tmax 0.862, 1.000 0.908, 1.000
No. of measured, independent and observed reflections 10089, 4366, 3457 [I > 2σ(I)] 8710, 3589, 3325 [I ≥ 2u(I)]
Rint 0.026 0.018
(sin θ/λ)max (Å−1) 0.601 0.601
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.047, 0.133, 1.06 0.033, 0.087, 1.04
No. of reflections 4366 3589
No. of parameters 382 268
No. of restraints 282 0
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) 0.38, −0.39 0.27, −0.21
Computer programs: CrysAlis PRO (Rigaku OD, 2022[Rigaku OD (2022). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]), SHELXT2018/2 (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXL2019/2 (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]), OLEX2.refine (Bourhis et al., 2015[Bourhis, L. J., Dolomanov, O. V., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2015). Acta Cryst. A71, 59-75.]) and OLEX2 (Dolomanov et al., 2009[Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339-341.]).

Supporting information

CCDC references: 2312143; 2312144

Crystal structure: contains datablocks II, I. DOI: https://doi.org/10.1107/S2056989024009794/ox2007sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989024009794/ox2007Isup2.hkl

Structure factors: contains datablock II. DOI: https://doi.org/10.1107/S2056989024009794/ox2007IIsup3.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989024009794/ox2007Isup4.mol

Supporting information file. DOI: https://doi.org/10.1107/S2056989024009794/ox2007IIsup5.mol

Supporting information file. DOI: https://doi.org/10.1107/S2056989024009794/ox2007Isup6.cml

Supporting information file. DOI: https://doi.org/10.1107/S2056989024009794/ox2007IIsup7.cml

checkCIF report


Computing details top

1-(3,4-Dimethoxybenzyl)-6,7-dimethoxyisoquinoline–fumaric acid (2/1) (II) top
Crystal data top
C20H21NO4·0.5C4H4O4F(000) = 843.079
Mr = 397.43Dx = 1.329 Mg m−3
Monoclinic, P21/nCu Kα radiation, λ = 1.54184 Å
a = 9.05718 (12) ÅCell parameters from 6957 reflections
b = 6.71363 (11) Åθ = 2.7–67.9°
c = 32.8419 (4) ŵ = 0.80 mm−1
β = 95.9308 (12)°T = 100 K
V = 1986.31 (5) Å3Block, clear light colourless
Z = 40.22 × 0.11 × 0.11 mm
Data collection top
XtaLAB Synergy, Single source at home/near, HyPix3000
diffractometer		3589 independent reflections
Radiation source: micro-focus sealed X-ray tube, PhotonJet (Cu) X-ray Source3325 reflections with I ≥ 2u(I)
Mirror monochromatorRint = 0.018
Detector resolution: 10.0000 pixels mm-1θmax = 68.0°, θmin = 2.7°
ω scansh = −10→5
Absorption correction: multi-scan
(CrysAlisPro; Rigaku OD, 2022)		k = −8→8
Tmin = 0.908, Tmax = 1.000l = −39→39
8710 measured reflections
Refinement top
Refinement on F237 constraints
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.033 w = 1/[σ2(Fo2) + (0.0429P)2 + 0.6045P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.087(Δ/σ)max = −0.0003
S = 1.04Δρmax = 0.27 e Å−3
3589 reflectionsΔρmin = −0.21 e Å−3
268 parametersExtinction correction: SHELXL2019/2 (Sheldrick, 2015b), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
0 restraintsExtinction coefficient: 0.0012 (2)
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
N10.51693 (10)0.60177 (14)0.44622 (3)0.0210 (2)
C20.60617 (12)0.51334 (17)0.42229 (3)0.0187 (2)
C30.74048 (11)0.60359 (17)0.41307 (3)0.0182 (2)
C40.83390 (12)0.51426 (17)0.38613 (3)0.0197 (2)
H40.80587 (12)0.39140 (17)0.37322 (3)0.0237 (3)*
C50.96396 (12)0.60367 (18)0.37863 (3)0.0218 (2)
C61.00943 (13)0.78635 (18)0.39912 (3)0.0238 (3)
C70.92008 (13)0.87524 (17)0.42489 (3)0.0229 (3)
H70.94998 (13)0.99708 (17)0.43796 (3)0.0274 (3)*
C80.78282 (12)0.78679 (17)0.43229 (3)0.0200 (2)
C90.68699 (13)0.87280 (17)0.45879 (3)0.0227 (2)
H90.71313 (13)0.99387 (17)0.47268 (3)0.0272 (3)*
C100.55693 (13)0.77991 (18)0.46414 (3)0.0233 (3)
H100.49118 (13)0.84156 (18)0.48104 (3)0.0279 (3)*
C110.56339 (12)0.30741 (17)0.40725 (3)0.0206 (2)
H11a0.47821 (12)0.26165 (17)0.42142 (3)0.0247 (3)*
H11b0.64743 (12)0.21623 (17)0.41512 (3)0.0247 (3)*
C120.52185 (11)0.29044 (16)0.36140 (3)0.0192 (2)
C130.58166 (12)0.13608 (17)0.33954 (3)0.0205 (2)
H130.64718 (12)0.04275 (17)0.35364 (3)0.0246 (3)*
C140.54649 (12)0.11766 (17)0.29756 (3)0.0208 (2)
C150.44833 (11)0.25584 (17)0.27672 (3)0.0200 (2)
C160.38820 (12)0.40628 (17)0.29850 (4)0.0223 (2)
H160.32136 (12)0.49876 (17)0.28463 (4)0.0268 (3)*
C170.42478 (12)0.42374 (17)0.34077 (4)0.0219 (2)
H170.38266 (12)0.52785 (17)0.35539 (4)0.0262 (3)*
O180.60006 (10)−0.02676 (13)0.27362 (3)0.0286 (2)
C190.70127 (16)−0.1679 (2)0.29353 (4)0.0363 (3)
H19a0.7335 (9)−0.2609 (10)0.27322 (6)0.0545 (5)*
H19b0.7878 (6)−0.0977 (3)0.3070 (3)0.0545 (5)*
H19c0.6519 (4)−0.2418 (11)0.3140 (2)0.0545 (5)*
O200.41893 (9)0.22626 (12)0.23544 (2)0.0241 (2)
C210.32565 (14)0.37026 (19)0.21353 (4)0.0291 (3)
H21a0.3150 (9)0.3372 (8)0.18431 (5)0.0436 (4)*
H21b0.2278 (4)0.3696 (10)0.2238 (2)0.0436 (4)*
H21c0.3702 (6)0.5028 (3)0.2175 (2)0.0436 (4)*
O221.05851 (9)0.53419 (14)0.35250 (3)0.0282 (2)
C231.00672 (13)0.37103 (19)0.32693 (4)0.0289 (3)
H23a1.0801 (5)0.3403 (9)0.3079 (2)0.0433 (4)*
H23b0.9924 (10)0.2541 (4)0.34395 (4)0.0433 (4)*
H23c0.9122 (5)0.4069 (5)0.3114 (2)0.0433 (4)*
O241.14269 (9)0.85526 (14)0.39014 (3)0.0324 (2)
C251.20004 (16)1.0296 (2)0.41170 (4)0.0373 (3)
H25a1.2970 (6)1.0637 (10)0.4028 (3)0.0559 (5)*
H25b1.1312 (6)1.1410 (5)0.4058 (3)0.0559 (5)*
H25c1.2110 (12)1.0031 (6)0.44120 (5)0.0559 (5)*
C300.18953 (12)0.55150 (17)0.48065 (3)0.0206 (2)
O310.26149 (9)0.45088 (13)0.45496 (3)0.0256 (2)
H310.3443 (7)0.5047 (14)0.4531 (4)0.0384 (3)*
O320.23373 (9)0.70574 (13)0.49758 (3)0.0272 (2)
C330.04511 (12)0.45913 (17)0.48787 (3)0.0213 (2)
H330.01702 (12)0.33727 (17)0.47454 (3)0.0256 (3)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0193 (4)0.0212 (5)0.0225 (5)−0.0011 (4)0.0023 (4)−0.0005 (4)
C20.0174 (5)0.0194 (6)0.0189 (5)−0.0011 (4)−0.0002 (4)0.0019 (4)
C30.0178 (5)0.0175 (5)0.0188 (5)−0.0022 (4)−0.0011 (4)0.0029 (4)
C40.0191 (5)0.0184 (5)0.0213 (5)−0.0041 (4)0.0002 (4)0.0003 (4)
C50.0196 (5)0.0252 (6)0.0207 (5)−0.0036 (5)0.0024 (4)0.0016 (5)
C60.0226 (6)0.0275 (6)0.0209 (5)−0.0114 (5)0.0002 (4)0.0043 (5)
C70.0271 (6)0.0196 (6)0.0209 (5)−0.0084 (5)−0.0022 (4)0.0012 (4)
C80.0227 (5)0.0175 (6)0.0189 (5)−0.0024 (4)−0.0025 (4)0.0035 (4)
C90.0280 (6)0.0178 (6)0.0214 (5)−0.0016 (5)−0.0012 (4)−0.0014 (4)
C100.0251 (6)0.0211 (6)0.0236 (6)0.0010 (5)0.0024 (4)−0.0019 (5)
C110.0183 (5)0.0190 (6)0.0250 (6)−0.0048 (4)0.0041 (4)0.0004 (4)
C120.0144 (5)0.0185 (5)0.0251 (6)−0.0061 (4)0.0034 (4)−0.0014 (4)
C130.0163 (5)0.0178 (5)0.0272 (6)−0.0009 (4)0.0014 (4)0.0009 (4)
C140.0180 (5)0.0177 (5)0.0271 (6)0.0001 (4)0.0045 (4)−0.0026 (4)
C150.0172 (5)0.0194 (5)0.0234 (5)−0.0031 (4)0.0022 (4)−0.0007 (4)
C160.0180 (5)0.0195 (6)0.0290 (6)0.0011 (4)0.0006 (4)0.0001 (5)
C170.0185 (5)0.0192 (6)0.0282 (6)−0.0003 (4)0.0040 (4)−0.0046 (5)
O180.0330 (4)0.0255 (4)0.0267 (4)0.0120 (4)0.0012 (3)−0.0044 (3)
C190.0401 (7)0.0313 (7)0.0368 (7)0.0189 (6)0.0001 (6)−0.0051 (6)
O200.0265 (4)0.0225 (4)0.0228 (4)0.0041 (3)0.0006 (3)−0.0012 (3)
C210.0370 (7)0.0237 (6)0.0259 (6)0.0057 (5)0.0000 (5)0.0030 (5)
O220.0229 (4)0.0333 (5)0.0300 (4)−0.0099 (4)0.0098 (3)−0.0059 (4)
C230.0282 (6)0.0286 (7)0.0314 (6)−0.0063 (5)0.0111 (5)−0.0056 (5)
O240.0281 (4)0.0398 (5)0.0303 (4)−0.0218 (4)0.0071 (3)−0.0050 (4)
C250.0372 (7)0.0431 (8)0.0313 (6)−0.0279 (6)0.0021 (5)−0.0028 (6)
C300.0217 (5)0.0200 (6)0.0200 (5)−0.0001 (4)0.0019 (4)0.0010 (4)
O310.0217 (4)0.0257 (4)0.0307 (4)−0.0044 (3)0.0092 (3)−0.0064 (3)
O320.0252 (4)0.0246 (5)0.0326 (4)−0.0063 (3)0.0071 (3)−0.0078 (4)
C330.0223 (5)0.0197 (6)0.0218 (5)−0.0019 (4)0.0014 (4)−0.0011 (4)
Geometric parameters (Å, º) top
N1—C21.3245 (14)C15—C161.3817 (16)
N1—C101.3652 (15)C15—O201.3688 (13)
C2—C31.4195 (15)C16—H160.9500
C2—C111.5053 (15)C16—C171.3984 (16)
C3—C41.4187 (16)C17—H170.9500
C3—C81.4172 (16)O18—C191.4288 (15)
C4—H40.9500C19—H19a0.9800
C4—C51.3670 (15)C19—H19b0.9800
C5—C61.4386 (17)C19—H19c0.9800
C5—O221.3561 (14)O20—C211.4285 (14)
C6—C71.3670 (17)C21—H21a0.9800
C6—O241.3533 (14)C21—H21b0.9800
C7—H70.9500C21—H21c0.9800
C7—C81.4211 (16)O22—C231.4296 (15)
C8—C91.4145 (16)C23—H23a0.9800
C9—H90.9500C23—H23b0.9800
C9—C101.3602 (17)C23—H23c0.9800
C10—H100.9500O24—C251.4372 (15)
C11—H11a0.9900C25—H25a0.9800
C11—H11b0.9900C25—H25b0.9800
C11—C121.5183 (15)C25—H25c0.9800
C12—C131.4011 (16)C30—O311.3064 (14)
C12—C171.3819 (16)C30—O321.2230 (14)
C13—H130.9500C30—C331.4884 (16)
C13—C141.3880 (16)O31—H310.8400
C14—C151.4120 (16)C33—C33i1.319 (2)
C14—O181.3684 (14)C33—H330.9500
C10—N1—C2119.83 (10)C16—C15—C14119.43 (10)
C3—C2—N1121.62 (10)O20—C15—C14115.67 (10)
C11—C2—N1117.02 (9)O20—C15—C16124.90 (10)
C11—C2—C3121.27 (10)H16—C16—C15119.68 (7)
C4—C3—C2122.15 (10)C17—C16—C15120.64 (10)
C8—C3—C2118.28 (10)C17—C16—H16119.68 (7)
C8—C3—C4119.55 (10)C16—C17—C12120.38 (10)
H4—C4—C3119.75 (6)H17—C17—C12119.81 (7)
C5—C4—C3120.49 (10)H17—C17—C16119.81 (7)
C5—C4—H4119.75 (7)C19—O18—C14117.12 (9)
C6—C5—C4120.02 (10)H19a—C19—O18109.5
O22—C5—C4125.12 (11)H19b—C19—O18109.5
O22—C5—C6114.86 (10)H19b—C19—H19a109.5
C7—C6—C5120.18 (10)H19c—C19—O18109.5
O24—C6—C5114.08 (10)H19c—C19—H19a109.5
O24—C6—C7125.74 (11)H19c—C19—H19b109.5
H7—C7—C6119.75 (7)C21—O20—C15116.43 (9)
C8—C7—C6120.51 (10)H21a—C21—O20109.5
C8—C7—H7119.75 (7)H21b—C21—O20109.5
C7—C8—C3119.20 (10)H21b—C21—H21a109.5
C9—C8—C3118.26 (10)H21c—C21—O20109.5
C9—C8—C7122.54 (10)H21c—C21—H21a109.5
H9—C9—C8120.43 (6)H21c—C21—H21b109.5
C10—C9—C8119.14 (10)C23—O22—C5116.42 (9)
C10—C9—H9120.43 (7)H23a—C23—O22109.5
C9—C10—N1122.73 (11)H23b—C23—O22109.5
H10—C10—N1118.63 (6)H23b—C23—H23a109.5
H10—C10—C9118.63 (7)H23c—C23—O22109.5
H11a—C11—C2108.51 (6)H23c—C23—H23a109.5
H11b—C11—C2108.51 (6)H23c—C23—H23b109.5
H11b—C11—H11a107.5C25—O24—C6117.14 (10)
C12—C11—C2115.05 (9)H25a—C25—O24109.5
C12—C11—H11a108.51 (5)H25b—C25—O24109.5
C12—C11—H11b108.51 (6)H25b—C25—H25a109.5
C13—C12—C11119.63 (10)H25c—C25—O24109.5
C17—C12—C11121.16 (10)H25c—C25—H25a109.5
C17—C12—C13119.20 (10)H25c—C25—H25b109.5
H13—C13—C12119.55 (6)O32—C30—O31124.73 (10)
C14—C13—C12120.90 (10)C33—C30—O31113.12 (10)
C14—C13—H13119.55 (7)C33—C30—O32122.15 (10)
C15—C14—C13119.43 (10)H31—O31—C30109.5
O18—C14—C13125.11 (10)C33i—C33—C30122.17 (13)
O18—C14—C15115.46 (10)H33—C33—C30118.91 (6)
N1—C2—C3—C4−177.32 (10)C5—C6—C7—C81.10 (13)
N1—C2—C3—C84.06 (12)C5—C6—O24—C25−175.75 (11)
N1—C2—C11—C12113.81 (10)C6—C7—C8—C9179.76 (11)
N1—C10—C9—C82.72 (13)C7—C8—C9—C10179.60 (11)
C2—C3—C4—C5−178.66 (11)C11—C12—C13—C14−179.55 (10)
C2—C3—C8—C7177.22 (10)C11—C12—C17—C16179.76 (10)
C2—C3—C8—C9−1.70 (12)C12—C13—C14—C15−0.40 (12)
C2—C11—C12—C13133.10 (9)C12—C13—C14—O18179.50 (10)
C2—C11—C12—C17−47.48 (11)C12—C17—C16—C150.01 (13)
C3—C4—C5—C62.05 (12)C13—C14—C15—C16−0.41 (12)
C3—C4—C5—O22−177.78 (10)C13—C14—C15—O20−179.63 (10)
C3—C8—C7—C60.89 (12)C13—C14—O18—C19−0.69 (14)
C3—C8—C9—C10−1.52 (12)C14—C15—C16—C170.61 (12)
C4—C5—C6—C7−2.60 (13)C14—C15—O20—C21−177.02 (10)
C4—C5—C6—O24177.69 (11)C30—C33—C33i—C30i180.00 (14)
C4—C5—O22—C239.21 (14)
Symmetry code: (i) −x, −y+1, −z+1.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O31—H31···N10.84 (1)1.73 (1)2.5687 (12)175 (1)
C9—H9···O32ii0.95 (1)2.27 (1)3.2191 (14)176 (1)
Symmetry code: (ii) −x+1, −y+2, −z+1.
1-(3,4-Dimethoxybenzyl)-6,7-dimethoxyisoquinoline–fumaric acid (2/3) (I) top
Crystal data top
C20H22NO4·1.5C4H4O4Z = 2
Mr = 513.48F(000) = 540
Triclinic, P1Dx = 1.405 Mg m−3
a = 9.5290 (2) ÅCu Kα radiation, λ = 1.54184 Å
b = 10.5445 (3) ÅCell parameters from 6061 reflections
c = 12.6509 (4) Åθ = 3.6–68.1°
α = 91.606 (2)°µ = 0.92 mm−1
β = 104.980 (2)°T = 100 K
γ = 97.823 (2)°Block, clear light colourless
V = 1213.87 (6) Å30.17 × 0.08 × 0.03 mm
Data collection top
XtaLAB Synergy, Single source at home/near, HyPix3000
diffractometer		4366 independent reflections
Radiation source: micro-focus sealed X-ray tube, PhotonJet (Cu) X-ray Source3457 reflections with I > 2σ(I)
Mirror monochromatorRint = 0.026
Detector resolution: 10.0000 pixels mm-1θmax = 68.0°, θmin = 3.6°
ω scansh = −11→5
Absorption correction: multi-scan
(CrysAlisPro; Rigaku OD, 2022)		k = −12→12
Tmin = 0.862, Tmax = 1.000l = −15→15
10089 measured reflections
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)] = 0.047 w = 1/[σ2(Fo2) + (0.0609P)2 + 0.410P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.133(Δ/σ)max < 0.001
S = 1.06Δρmax = 0.38 e Å−3
4366 reflectionsΔρmin = −0.39 e Å−3
382 parametersExtinction correction: SHELXL2019/2 (Sheldrick, 2015b), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
282 restraintsExtinction coefficient: 0.0009 (3)
Primary atom site location: structure-invariant direct methods
Special details top

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

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/UeqOcc. (<1)
N10.46197 (17)0.81758 (17)0.51609 (18)0.0444 (5)
H10.5436850.8502360.5004660.053*
C20.3393 (2)0.79572 (18)0.43509 (19)0.0359 (5)
C30.20717 (19)0.74256 (17)0.45885 (17)0.0303 (4)
C40.07358 (18)0.71542 (17)0.37492 (16)0.0286 (4)
H40.0730220.7300350.3010670.034*
C5−0.05396 (18)0.66853 (17)0.39956 (16)0.0289 (4)
C6−0.05444 (19)0.64893 (17)0.51115 (17)0.0301 (4)
C70.0738 (2)0.67300 (17)0.59334 (17)0.0326 (4)
H70.0727470.6591660.6670340.039*
C80.2077 (2)0.71842 (17)0.56852 (17)0.0320 (4)
C90.3442 (2)0.7438 (2)0.6496 (2)0.0430 (5)
H90.3490810.7267780.7236800.052*
C100.4681 (2)0.7924 (2)0.6211 (2)0.0492 (6)
H100.5594260.8087560.6754120.059*
C110.3489 (2)0.83103 (18)0.3232 (2)0.0404 (5)
H11A0.4402870.8915770.3301940.049*
H11B0.2649710.8757060.2895280.049*
C120.3477 (2)0.71580 (18)0.24786 (19)0.0356 (5)
C130.2463 (2)0.69676 (18)0.14486 (19)0.0359 (5)
H130.1769600.7543040.1239550.043*
C140.2456 (2)0.59499 (19)0.07283 (18)0.0352 (4)
C150.3481 (2)0.50903 (18)0.10481 (17)0.0338 (4)
C160.4475 (2)0.52812 (18)0.20657 (17)0.0342 (4)
H160.5159800.4700310.2283770.041*
C170.4487 (2)0.63203 (18)0.27815 (18)0.0343 (4)
H170.5188930.6450610.3475930.041*
O180.15271 (16)0.56999 (14)−0.02976 (13)0.0416 (4)
C190.0454 (2)0.6537 (2)−0.0642 (2)0.0451 (5)
H19A−0.0180090.622919−0.1370130.068*
H19B0.0951570.740628−0.0674950.068*
H19C−0.0142980.654835−0.0118160.068*
O200.33975 (16)0.41301 (14)0.02746 (12)0.0415 (4)
C210.4403 (3)0.3231 (2)0.05620 (19)0.0458 (5)
H21A0.4296160.263692−0.0073010.069*
H21B0.4194710.2748270.1168460.069*
H21C0.5409780.3690630.0788160.069*
O22−0.18676 (13)0.63998 (14)0.32630 (12)0.0370 (3)
C23−0.1929 (2)0.6669 (3)0.21502 (19)0.0514 (6)
H23A−0.2950600.6492920.1705100.077*
H23B−0.1337120.6125630.1863780.077*
H23C−0.1542340.7573650.2120150.077*
O24−0.18929 (14)0.60799 (13)0.52392 (12)0.0375 (3)
C25−0.2027 (3)0.6004 (2)0.63391 (19)0.0451 (5)
H25A−0.3058540.5738980.6323340.068*
H25B−0.1677560.6846780.6736160.068*
H25C−0.1434860.5375230.6709960.068*
C340.6558 (2)1.03159 (19)0.13490 (18)0.0369 (5)
O350.60430 (18)0.93880 (15)0.18930 (13)0.0484 (4)
H350.6544200.9462790.2549740.073*
O360.76487 (17)1.10891 (15)0.17335 (14)0.0477 (4)
C370.5660 (2)1.03429 (18)0.02071 (18)0.0368 (5)
H370.6054531.088822−0.0263670.044*
C380.9160 (2)0.9597 (2)0.8450 (2)0.0504 (6)
O39A0.9425 (5)1.0085 (3)0.7594 (3)0.0410 (9)0.598 (9)
H39A0.8836960.9694760.7030760.062*0.598 (9)
O39B0.9637 (9)1.0502 (9)0.7980 (9)0.091 (3)0.402 (9)
O40A0.8223 (6)0.8669 (5)0.8449 (3)0.0554 (11)0.598 (9)
O40B0.8172 (9)0.8612 (7)0.8033 (9)0.095 (3)0.402 (9)
H40B0.804 (10)0.868 (7)0.7354 (12)0.142*0.402 (9)
C41A1.0105 (5)1.0188 (5)0.9512 (4)0.0314 (11)0.598 (9)
H41A1.0885801.0852830.9514500.038*0.598 (9)
C41B0.9522 (9)0.9608 (9)0.9704 (8)0.047 (2)0.402 (9)
H41B0.8981440.8982301.0029130.057*0.402 (9)
C300.7944 (2)0.94153 (17)0.48749 (18)0.0334 (4)
O310.69127 (18)0.92626 (15)0.40213 (14)0.0491 (4)
O320.77542 (17)0.91662 (14)0.57896 (13)0.0448 (4)
C33A0.9361 (4)0.9954 (2)0.4628 (4)0.0278 (11)0.742 (11)
H33A0.9336671.0237210.3918220.033*0.742 (11)
C33B0.9632 (11)0.9786 (7)0.5352 (10)0.030 (3)0.258 (11)
H33B1.0104350.9711080.6102350.036*0.258 (11)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0222 (8)0.0367 (9)0.0710 (14)0.0039 (6)0.0085 (8)−0.0155 (9)
C20.0237 (9)0.0261 (9)0.0583 (13)0.0035 (7)0.0131 (9)−0.0100 (8)
C30.0228 (8)0.0239 (8)0.0446 (12)0.0056 (6)0.0094 (8)−0.0053 (8)
C40.0246 (8)0.0280 (9)0.0347 (10)0.0044 (7)0.0105 (8)−0.0023 (7)
C50.0223 (8)0.0281 (9)0.0354 (10)0.0033 (7)0.0072 (7)−0.0049 (7)
C60.0272 (9)0.0252 (9)0.0406 (11)0.0032 (7)0.0145 (8)−0.0021 (8)
C70.0372 (10)0.0276 (9)0.0349 (11)0.0093 (7)0.0107 (8)0.0002 (8)
C80.0286 (9)0.0263 (9)0.0402 (11)0.0097 (7)0.0052 (8)−0.0047 (8)
C90.0397 (11)0.0355 (11)0.0476 (13)0.0164 (8)−0.0039 (9)−0.0101 (9)
C100.0257 (10)0.0407 (12)0.0709 (17)0.0117 (8)−0.0066 (10)−0.0190 (11)
C110.0317 (10)0.0281 (9)0.0681 (15)−0.0007 (7)0.0282 (10)−0.0027 (9)
C120.0284 (9)0.0271 (9)0.0590 (14)0.0022 (7)0.0260 (9)0.0019 (9)
C130.0296 (9)0.0301 (9)0.0567 (13)0.0094 (7)0.0236 (9)0.0100 (9)
C140.0332 (10)0.0347 (10)0.0450 (12)0.0082 (8)0.0211 (9)0.0106 (8)
C150.0362 (10)0.0319 (9)0.0418 (12)0.0106 (8)0.0218 (9)0.0071 (8)
C160.0334 (9)0.0323 (10)0.0445 (12)0.0113 (7)0.0199 (9)0.0060 (8)
C170.0270 (9)0.0332 (10)0.0475 (12)0.0029 (7)0.0197 (8)0.0002 (8)
O180.0433 (8)0.0432 (8)0.0438 (9)0.0172 (6)0.0150 (7)0.0102 (7)
C190.0401 (11)0.0467 (12)0.0550 (14)0.0166 (9)0.0175 (10)0.0168 (11)
O200.0536 (8)0.0386 (8)0.0389 (8)0.0213 (7)0.0164 (7)0.0036 (6)
C210.0624 (14)0.0410 (12)0.0420 (13)0.0261 (10)0.0182 (11)0.0036 (10)
O220.0212 (6)0.0521 (8)0.0353 (8)0.0007 (5)0.0062 (5)−0.0040 (6)
C230.0283 (10)0.0872 (18)0.0347 (12)0.0023 (10)0.0051 (9)0.0011 (12)
O240.0320 (7)0.0389 (7)0.0457 (9)−0.0017 (5)0.0213 (6)−0.0004 (6)
C250.0530 (13)0.0430 (12)0.0507 (14)0.0094 (10)0.0322 (11)0.0067 (10)
C340.0422 (11)0.0301 (10)0.0452 (12)0.0068 (8)0.0227 (9)0.0024 (8)
O350.0550 (9)0.0476 (9)0.0401 (9)−0.0056 (7)0.0147 (7)0.0075 (7)
O360.0445 (8)0.0464 (9)0.0528 (10)−0.0001 (7)0.0169 (7)0.0068 (7)
C370.0462 (11)0.0294 (9)0.0420 (12)0.0073 (8)0.0237 (9)0.0034 (8)
C380.0472 (13)0.0539 (14)0.0506 (15)0.0289 (11)0.0036 (11)−0.0042 (11)
O39A0.0466 (17)0.0416 (16)0.0310 (18)0.0077 (12)0.0045 (15)−0.0136 (12)
O39B0.069 (4)0.150 (6)0.068 (6)0.054 (5)0.020 (4)0.054 (5)
O40A0.079 (3)0.075 (3)0.0154 (18)0.0210 (18)0.0145 (19)0.0043 (17)
O40B0.086 (4)0.082 (4)0.082 (6)0.042 (3)−0.048 (4)−0.058 (4)
C41A0.034 (2)0.035 (2)0.031 (3)0.0118 (16)0.0154 (18)0.0083 (17)
C41B0.043 (4)0.050 (4)0.048 (5)0.021 (3)0.002 (3)0.005 (3)
C300.0262 (9)0.0246 (9)0.0509 (13)0.0034 (7)0.0140 (9)−0.0030 (8)
O310.0561 (9)0.0458 (9)0.0434 (9)0.0058 (7)0.0104 (8)0.0035 (7)
O320.0540 (9)0.0415 (8)0.0426 (9)0.0160 (7)0.0147 (7)0.0036 (7)
C33A0.0264 (19)0.0261 (13)0.032 (2)0.0037 (10)0.0103 (15)0.0011 (11)
C33B0.033 (5)0.026 (4)0.030 (7)0.006 (3)0.003 (3)0.001 (3)
Geometric parameters (Å, º) top
N1—H10.8800C21—H21A0.9800
N1—C21.328 (3)C21—H21B0.9800
N1—C101.350 (3)C21—H21C0.9800
C2—C31.415 (3)O22—C231.432 (3)
C2—C111.496 (3)C23—H23A0.9800
C3—C41.419 (3)C23—H23B0.9800
C3—C81.416 (3)C23—H23C0.9800
C4—H40.9500O24—C251.433 (3)
C4—C51.364 (3)C25—H25A0.9800
C5—C61.434 (3)C25—H25B0.9800
C5—O221.351 (2)C25—H25C0.9800
C6—C71.372 (3)C34—O351.324 (2)
C6—O241.351 (2)C34—O361.211 (3)
C7—H70.9500C34—C371.480 (3)
C7—C81.416 (3)O35—H350.8400
C8—C91.420 (3)C37—C37i1.331 (4)
C9—H90.9500C37—H370.9500
C9—C101.361 (4)C38—O39A1.280 (4)
C10—H100.9500C38—O39B1.235 (5)
C11—H11A0.9900C38—O40A1.231 (4)
C11—H11B0.9900C38—O40B1.300 (5)
C11—C121.520 (3)C38—C41A1.476 (6)
C12—C131.398 (3)C38—C41B1.533 (10)
C12—C171.383 (3)O39A—H39A0.8400
C13—H130.9500O40B—H40B0.843 (5)
C13—C141.386 (3)C41A—C41Aii1.362 (9)
C14—C151.413 (3)C41A—H41A0.9500
C14—O181.364 (3)C41B—C41Bii1.218 (17)
C15—C161.378 (3)C41B—H41B0.9500
C15—O201.368 (2)C30—O311.248 (3)
C16—H160.9500C30—O321.246 (3)
C16—C171.399 (3)C30—C33A1.504 (3)
C17—H170.9500C30—C33B1.555 (10)
O18—C191.432 (2)C33A—C33Aiii1.322 (8)
C19—H19A0.9800C33A—H33A0.9500
C19—H19B0.9800C33B—C33Biii1.32 (2)
C19—H19C0.9800C33B—H33B0.9500
O20—C211.427 (2)
C2—N1—H1118.2O18—C19—H19C109.5
C2—N1—C10123.56 (18)H19A—C19—H19B109.5
C10—N1—H1118.2H19A—C19—H19C109.5
N1—C2—C3118.9 (2)H19B—C19—H19C109.5
N1—C2—C11117.53 (17)C15—O20—C21116.92 (17)
C3—C2—C11123.60 (18)O20—C21—H21A109.5
C2—C3—C4121.08 (19)O20—C21—H21B109.5
C2—C3—C8119.45 (18)O20—C21—H21C109.5
C8—C3—C4119.47 (16)H21A—C21—H21B109.5
C3—C4—H4119.8H21A—C21—H21C109.5
C5—C4—C3120.47 (18)H21B—C21—H21C109.5
C5—C4—H4119.8C5—O22—C23116.43 (14)
C4—C5—C6120.03 (17)O22—C23—H23A109.5
O22—C5—C4125.26 (18)O22—C23—H23B109.5
O22—C5—C6114.68 (15)O22—C23—H23C109.5
C7—C6—C5120.41 (16)H23A—C23—H23B109.5
O24—C6—C5113.56 (16)H23A—C23—H23C109.5
O24—C6—C7126.02 (18)H23B—C23—H23C109.5
C6—C7—H7119.9C6—O24—C25117.25 (16)
C6—C7—C8120.11 (19)O24—C25—H25A109.5
C8—C7—H7119.9O24—C25—H25B109.5
C3—C8—C9117.70 (18)O24—C25—H25C109.5
C7—C8—C3119.43 (17)H25A—C25—H25B109.5
C7—C8—C9122.9 (2)H25A—C25—H25C109.5
C8—C9—H9120.0H25B—C25—H25C109.5
C10—C9—C8120.0 (2)O35—C34—C37113.63 (18)
C10—C9—H9120.0O36—C34—O35124.4 (2)
N1—C10—C9120.4 (2)O36—C34—C37121.98 (19)
N1—C10—H10119.8C34—O35—H35109.5
C9—C10—H10119.8C34—C37—H37117.7
C2—C11—H11A109.0C37i—C37—C34124.6 (2)
C2—C11—H11B109.0C37i—C37—H37117.7
C2—C11—C12113.08 (16)O39A—C38—C41A116.0 (3)
H11A—C11—H11B107.8O39B—C38—O40B128.8 (6)
C12—C11—H11A109.0O39B—C38—C41B121.7 (6)
C12—C11—H11B109.0O40A—C38—O39A125.4 (3)
C13—C12—C11119.44 (18)O40A—C38—C41A118.6 (3)
C17—C12—C11121.0 (2)O40B—C38—C41B108.9 (6)
C17—C12—C13119.51 (19)C38—O39A—H39A109.5
C12—C13—H13119.6C38—O40B—H40B102 (4)
C14—C13—C12120.86 (18)C38—C41A—H41A118.9
C14—C13—H13119.6C41Aii—C41A—C38122.3 (7)
C13—C14—C15119.3 (2)C41Aii—C41A—H41A118.9
O18—C14—C13125.05 (18)C38—C41B—H41B118.9
O18—C14—C15115.65 (18)C41Bii—C41B—C38122.2 (15)
C16—C15—C14119.54 (19)C41Bii—C41B—H41B118.9
O20—C15—C14114.80 (19)O31—C30—C33A110.7 (2)
O20—C15—C16125.64 (17)O31—C30—C33B145.1 (5)
C15—C16—H16119.6O32—C30—O31122.17 (17)
C15—C16—C17120.76 (18)O32—C30—C33A127.1 (2)
C17—C16—H16119.6O32—C30—C33B92.6 (5)
C12—C17—C16120.0 (2)C30—C33A—H33A119.1
C12—C17—H17120.0C33Aiii—C33A—C30121.9 (4)
C16—C17—H17120.0C33Aiii—C33A—H33A119.1
C14—O18—C19117.23 (17)C30—C33B—H33B122.1
O18—C19—H19A109.5C33Biii—C33B—C30115.7 (13)
O18—C19—H19B109.5C33Biii—C33B—H33B122.1
N1—C2—C3—C4−178.96 (16)C11—C12—C13—C14177.90 (16)
N1—C2—C3—C82.3 (3)C11—C12—C17—C16−178.71 (16)
N1—C2—C11—C12103.3 (2)C12—C13—C14—C150.6 (3)
C2—N1—C10—C9−1.0 (3)C12—C13—C14—O18−178.84 (17)
C2—C3—C4—C5−177.63 (17)C13—C12—C17—C16−0.9 (3)
C2—C3—C8—C7175.96 (16)C13—C14—C15—C16−0.4 (3)
C2—C3—C8—C9−2.8 (3)C13—C14—C15—O20−179.14 (16)
C2—C11—C12—C13127.20 (19)C13—C14—O18—C19−1.7 (3)
C2—C11—C12—C17−55.0 (2)C14—C15—C16—C17−0.5 (3)
C3—C2—C11—C12−77.7 (2)C14—C15—O20—C21−179.53 (17)
C3—C4—C5—C61.4 (3)C15—C14—O18—C19178.86 (16)
C3—C4—C5—O22179.76 (16)C15—C16—C17—C121.1 (3)
C3—C8—C9—C101.5 (3)C16—C15—O20—C211.8 (3)
C4—C3—C8—C7−2.8 (3)C17—C12—C13—C140.1 (3)
C4—C3—C8—C9178.42 (16)O18—C14—C15—C16179.10 (16)
C4—C5—C6—C7−2.2 (3)O18—C14—C15—O200.3 (2)
C4—C5—C6—O24177.01 (16)O20—C15—C16—C17178.15 (16)
C4—C5—O22—C23−2.8 (3)O22—C5—C6—C7179.25 (16)
C5—C6—C7—C80.5 (3)O22—C5—C6—O24−1.5 (2)
C5—C6—O24—C25−172.83 (16)O24—C6—C7—C8−178.63 (17)
C6—C5—O22—C23175.66 (18)O35—C34—C37—C37i10.4 (3)
C6—C7—C8—C32.0 (3)O36—C34—C37—C37i−168.9 (2)
C6—C7—C8—C9−179.28 (17)O39A—C38—C41A—C41Aii176.4 (4)
C7—C6—O24—C256.3 (3)O39B—C38—C41B—C41Bii−12.6 (10)
C7—C8—C9—C10−177.25 (18)O40A—C38—C41A—C41Aii−5.6 (6)
C8—C3—C4—C51.1 (3)O40B—C38—C41B—C41Bii175.7 (8)
C8—C9—C10—N10.4 (3)O31—C30—C33A—C33Aiii−171.1 (3)
C10—N1—C2—C3−0.3 (3)O31—C30—C33B—C33Biii7.3 (12)
C10—N1—C2—C11178.75 (18)O32—C30—C33A—C33Aiii10.5 (4)
C11—C2—C3—C42.0 (3)O32—C30—C33B—C33Biii−176.6 (8)
C11—C2—C3—C8−176.73 (16)
Symmetry codes: (i) −x+1, −y+2, −z; (ii) −x+2, −y+2, −z+2; (iii) −x+2, −y+2, −z+1.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O310.882.203.034 (3)159
N1—H1···O320.882.182.919 (2)141
O35—H35···O310.841.832.617 (2)156
O39A—H39A···O320.841.672.502 (4)169
Selected geometric parameters (Å) for fumaric acid A, B, and C in compound (I) top
C30–O311.248 (2)
C30–O321.246 (3)
C34–O351.324 (3)
C34–O361.211 (2)
C38–O39Aa1.280 (5)
C38–O40Aa1.231 (6)

Acknowledgements

The authors thank Ayano Horikawa (Chugai Pharmaceutical Co., Ltd.) for helpful discussions of the single-crystal structure.

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ISSN: 2056-9890
Volume 80| Part 11| November 2024| Pages 1146-1150
https://doi.org/10.1107/S2056989024009794
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