Low-temperature study of a new nevirapine pseudopolymorph

Silva, C.C.P. da; Cuffini, S.L.; Faudone, S.N.; Ayala, A.P.; Ellena, J.

doi:10.1107/S1600536807042262

organic compounds

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ISSN: 2056-9890

Volume 64| Part 1| January 2008| Page o292

https://doi.org/10.1107/S1600536807042262

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Low-temperature study of a new nevirapine pseudopolymorph

C. C. P. da Silva,^a ^* S. L. Cuffini,^b S. N. Faudone,^b A. P. Ayala ^c and J. Ellena ^a

^aInstituto de Física de São Carlos, Universidade de São Paulo, FFI/Grupo de Cristalografia, Avenida Trabalhador Saocarlense 400, Brazil, ^bAgencia Córdoba Ciencia, Córdoba, Argentina, and ^cDepartamento de Física, UFC, Fortaleza, CE, Brazil
^*Correspondence e-mail: cecycarol@if.sc.usp.br

(Received 23 August 2007; accepted 28 August 2007; online 18 December 2007)

The title compound (systematic name: 11-cyclopropyl-4-methyl-5,11-dihydro-6H-dipyrido[3,2-b:2′,3′-e][1,4]diazepin-6-one butanol 0.3-solvate), C₁₅H₁₄N₄O·0.3C₄H₉OH, was crystallized in a new triclinic pseudopolymorphic form, a butanol solvate, and the crystal structure determined at 150 K. The molecular conformation of this new form differs from that reported previously, although the main intermolecular hydrogen-bond pattern remains the same. N—H⋯O hydrogen bonds [N⋯O = 2.957 (3) Å] form centrosymmetric dimers and the crystal packing of this new pseudopolymorph generates infinite channels along the b axis.

Related literature

For the crystal structure of an earlier polymorph, see: Mui et al. (1992 ). For spectroscopic studies of three further polymorphs, see: Reguri & Chakka (2005 ); World Health Organization (2005 ). For related literature, see: Ayala et al. (2007 ); Ren et al. (1995 ).

Experimental

Crystal data

C₁₅H₁₄N₄O·0.3C₄H₁₀O
M_r = 288.54
Triclinic, $[P \overline 1]$
a = 7.8116 (6) Å
b = 8.4302 (7) Å
c = 12.5451 (11) Å
α = 84.817 (5)°
β = 88.415 (5)°
γ = 68.252 (4)°
V = 764.18 (11) Å³
Z = 2
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 150.0 (2) K
0.47 × 0.29 × 0.07 mm

Data collection

Nonius KappaCCD area-detector diffractometer
Absorption correction: none
12941 measured reflections
3141 independent reflections
2295 reflections with I > 2σ(I)
R_int = 0.100

Refinement

R[F² > 2σ(F²)] = 0.075
wR(F²) = 0.237
S = 1.08
3141 reflections
222 parameters
28 restraints
H-atom parameters constrained
Δρ_max = 0.51 e Å⁻³
Δρ_min = −0.24 e Å⁻³

Data collection: COLLECT (Nonius, 2000 ); cell refinement: SCALEPACK (Otwinowski & Minor, 1997 ); data reduction: SCALEPACK and DENZO (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ); software used to prepare material for publication: WinGX (Farrugia, 1999 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S1600536807042262/bg2093sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536807042262/bg2093Isup2.hkl

checkCIF report

Comment top

Nevirapine (11-cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido[3,2 - b:2',3'-e][1,4]diazepin-6-one) (NVP) is an antiretroviral drug that belongs to the non-nucleoside inhibitors class of the HIV-1 virus reverse transcriptase (NNRTI). Only one crystal structure is known, reported by Mui et al., in the centrosymmetric space group, P2₁/c (Form I) [Mui et al., 1992]. The literature also describes the existence of two polymorphs (Form II and III), useful as anti-psychotics, and one hemihydrate pseudopolymorph (Form IV). They were studied by X-ray powder diffraction, RAMAN and IR, but no crystal structure studies are available yet [World Health Organization, 2005; Reguri & Chakka, 2005]. We report here, the crystal structure of the pseudopolymorph butanol solvate of nervirapine, C₁₅H₁₄N₄O*0.3(CH₃OH), in the centrosymmetric space group P1 (Figure 1), hereafter, Form V.

As most of the NNRTIs, nevirapine displays a "butterfly like" conformation, which is also preserved in complexes with the HIV-1 reverse transcriptase [Ren et al., 1995]. Comparing the NVP conformations, it could be seen that the dihedral angle between the least square planes through the pyridine rings is 123.89 (9)°, somewhat larger than the one found by Mui et al., 121°, but still smaller than the one determined from the enzyme-inhibitor complex structure and ab initio calculations (129.22°) [Ayala et al., 2007].

An electron delocalization effect is presented by the amide moiety of the 7-membered ring, allowing this group to adopt a planar conformation with a C6—C5—N2—C4 torsion angle of -2.7 (4)° (slightly smaller than the one found for I, -4°) and to which the cyclopropyl substituent, evolving away from the molecular framework, subtends a dihedral angle of 68.5 (1)°.

The molecular superposition of I and V, calculated by minimizing the root square distance between the atoms of the 7-membered rings, shows that the main conformational differences are mainly concentrated in the cyclopropyl group, which presents C14—C13—N4—C10 and C15—C13—N4—C11 torsion angles of 81.9 (3)°, -69.9 (3)° in V, and 74.6°, -78.1° in I, respectively. In addiction, the superposition shows a small difference in conformation of the methyl substituted pyridine ring. The asymmetric unit in V is completed by the presence of a disordered butanol molecule with an occupation factor of 0.3.

The analysis of the intermolecular interaction shows that, like in I, NEV molecules are linked essentially by two N—H···O hydrogen bonds, forming centrosymmetric dimers.

It is interesting to note that the main difference between both polymorphs is related to the crystal packing: while in I the intermolecular interaction generates a close packing with flat layers of nevirapine molecules separated by less than 4.4 Å, in V the three-dimensional arrangement generates infinite channels along de b axis with a diameter of more than 10.5 Å (Figure 2). These infinite channels are filled with highly disordered molecules of butanol, and this new Nevirapine form is stable even when a solvent occupation factor as low as 30%.

These findings indicate that a wide spectrum of new nevirapine pseudopolymorphs could be generated by just changing the solvent used in the crystallization process, as long as the volume of the solvent matches the available channel volume.

Related literature top

For the crystal structure of an earlier polymorph, see: Mui et al. (1992). For spectroscopic studies of three further polymorphs, see: Reguri & Chakka (2005); World Health Organization (2005). For related literature, see: Ayala et al. (2007); Ren et al. (1995).

Experimental top

NVP raw materials from different commercial sources were analyzed. USP standards of anhydrous and hemihydrate NEV were used as references.

Structure description top

The analysis of the intermolecular interaction shows that, like in I, NEV molecules are linked essentially by two N—H···O hydrogen bonds, forming centrosymmetric dimers.

For the crystal structure of an earlier polymorph, see: Mui et al. (1992). For spectroscopic studies of three further polymorphs, see: Reguri & Chakka (2005); World Health Organization (2005). For related literature, see: Ayala et al. (2007); Ren et al. (1995).

Computing details top

Data collection: COLLECT (Nonius, 2000); cell refinement: SCALEPACK (Otwinowski & Minor, 1997); data reduction: SCALEPACK (Otwinowski & Minor, 1997) and DENZO (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures top

	Fig. 1. The molecular structure of the butanol solvate of Nervirapine, showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level. H atoms are represented as small spheres of arbitrary radius.
	Fig. 2. Crystal packing of nevirapine, a) flat chain disposition of the molecules in Form I, and b) Channel formation with the solvent molecules inside.
	Fig. 3. Supplementary figure.

11-cyclopropyl-4-methyl-5,11-dihydro-6H-dipyrido[3,2 - b:2',3'-e][1,4] diazepin-6-one butanol 0.3-solvate top

Crystal data top

C₁₅H₁₄N₄O·0.3C₄H₁₀O	Z = 2
M_r = 288.54	F(000) = 305.2
Triclinic, P1	D_x = 1.254 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 7.8116 (6) Å	Cell parameters from 37940 reflections
b = 8.4302 (7) Å	θ = 2.9–26.4°
c = 12.5451 (11) Å	µ = 0.08 mm⁻¹
α = 84.817 (5)°	T = 150 K
β = 88.415 (5)°	Prism, colourless
γ = 68.252 (4)°	0.47 × 0.29 × 0.07 mm
V = 764.18 (11) Å³

Data collection top

Nonius KappaCCD area-detector diffractometer	2295 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.100
Horizonally mounted graphite crystal monochromator	θ_max = 26.8°, θ_min = 3.4°
Detector resolution: 9 pixels mm^-1	h = −9→9
φ scans and ω scans winth κ offsets	k = −10→10
12941 measured reflections	l = −15→15
3141 independent reflections

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.075	H-atom parameters constrained
wR(F²) = 0.237	w = 1/[σ²(F_o²) + (0.1266P)² + 0.361P] where P = (F_o² + 2F_c²)/3
S = 1.08	(Δ/σ)_max < 0.001
3141 reflections	Δρ_max = 0.51 e Å⁻³
222 parameters	Δρ_min = −0.24 e Å⁻³
28 restraints	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.37 (8)

Crystal data top

C₁₅H₁₄N₄O·0.3C₄H₁₀O	γ = 68.252 (4)°
M_r = 288.54	V = 764.18 (11) Å³
Triclinic, P1	Z = 2
a = 7.8116 (6) Å	Mo Kα radiation
b = 8.4302 (7) Å	µ = 0.08 mm⁻¹
c = 12.5451 (11) Å	T = 150 K
α = 84.817 (5)°	0.47 × 0.29 × 0.07 mm
β = 88.415 (5)°

Data collection top

Nonius KappaCCD area-detector diffractometer	2295 reflections with I > 2σ(I)
12941 measured reflections	R_int = 0.100
3141 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.075	28 restraints
wR(F²) = 0.237	H-atom parameters constrained
S = 1.08	Δρ_max = 0.51 e Å⁻³
3141 reflections	Δρ_min = −0.24 e Å⁻³
222 parameters

Special details top

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. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq	Occ. (<1)
C1	0.1486 (4)	1.0251 (4)	0.1362 (2)	0.0486 (7)
H1	0.0843	1.1222	0.0887	0.058*
C2	0.2621 (4)	1.0419 (4)	0.2131 (2)	0.0484 (7)
H2	0.2773	1.1481	0.2162	0.058*
C3	0.3543 (4)	0.9043 (3)	0.2859 (2)	0.0446 (7)
C4	0.3290 (4)	0.7507 (3)	0.27637 (19)	0.0413 (6)
C5	0.4871 (4)	0.4427 (3)	0.3419 (2)	0.0429 (7)
C6	0.4937 (4)	0.3825 (3)	0.23304 (19)	0.0412 (6)
C7	0.6468 (4)	0.2423 (3)	0.2073 (2)	0.0445 (7)
H7	0.7470	0.1928	0.2563	0.053*
C8	0.6523 (4)	0.1755 (4)	0.1104 (2)	0.0483 (7)
H8	0.7572	0.0819	0.0902	0.058*
C9	0.5019 (4)	0.2482 (4)	0.0438 (2)	0.0473 (7)
H9	0.5058	0.2010	−0.0226	0.057*
C10	0.3470 (4)	0.4485 (3)	0.15882 (19)	0.0398 (6)
C11	0.2150 (4)	0.7433 (3)	0.19405 (19)	0.0408 (6)
C12	0.4723 (5)	0.9217 (4)	0.3731 (2)	0.0544 (8)
H12A	0.4862	1.0328	0.3613	0.082*
H12B	0.5939	0.8294	0.3725	0.082*
H12C	0.4138	0.9142	0.4425	0.082*
C13	0.0187 (4)	0.6077 (3)	0.1266 (2)	0.0427 (6)
H13	0.0156	0.6333	0.0471	0.051*
C14	−0.0852 (4)	0.4999 (4)	0.1721 (2)	0.0513 (7)
H14A	−0.0327	0.4195	0.2358	0.062*
H14B	−0.1522	0.4595	0.1216	0.062*
C15	−0.1544 (4)	0.6888 (4)	0.1854 (2)	0.0550 (8)
H15A	−0.2643	0.7643	0.1433	0.066*
H15B	−0.1448	0.7244	0.2573	0.066*
N1	0.1247 (3)	0.8771 (3)	0.12553 (17)	0.0447 (6)
N2	0.4074 (3)	0.6114 (3)	0.35485 (16)	0.0438 (6)
H2A	0.4033	0.6390	0.4211	0.053*
N3	0.3494 (3)	0.3815 (3)	0.06598 (17)	0.0438 (6)
N4	0.1863 (3)	0.5888 (3)	0.18231 (16)	0.0406 (6)
O1	0.5584 (3)	0.3371 (2)	0.41782 (15)	0.0558 (6)
O1S	−0.0302 (14)	0.767 (2)	0.4857 (14)	0.151 (2)	0.30
H1S	−0.1389	0.8162	0.5006	0.227*	0.30
C1S	−0.0352 (18)	0.1631 (17)	0.4483 (10)	0.080 (3)	0.30
H11S	−0.1619	0.2166	0.4262	0.120*	0.30
H12S	−0.0245	0.0799	0.5077	0.120*	0.30
H13S	0.0377	0.1074	0.3899	0.120*	0.30
C2S	0.036 (2)	0.2730 (18)	0.4746 (9)	0.066 (3)	0.30
H21S	0.1625	0.1944	0.4872	0.079*	0.30
H22S	−0.0175	0.2782	0.5454	0.079*	0.30
C3S	0.0709 (18)	0.419 (2)	0.4881 (14)	0.109 (6)	0.30
H31S	0.1876	0.3703	0.5263	0.131*	0.30
H32S	0.1055	0.4342	0.4141	0.131*	0.30
C4S	0.019 (2)	0.578 (2)	0.5080 (18)	0.151 (2)	0.30
H41S	0.1126	0.5594	0.5620	0.182*	0.30
H42S	−0.0885	0.5808	0.5494	0.182*	0.30

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0560 (16)	0.0426 (15)	0.0444 (15)	−0.0156 (13)	0.0005 (12)	−0.0005 (11)
C2	0.0591 (17)	0.0413 (14)	0.0469 (15)	−0.0208 (13)	0.0056 (13)	−0.0067 (11)
C3	0.0519 (15)	0.0423 (14)	0.0412 (14)	−0.0189 (12)	0.0041 (11)	−0.0067 (11)
C4	0.0494 (15)	0.0394 (14)	0.0346 (12)	−0.0155 (11)	0.0021 (11)	−0.0050 (10)
C5	0.0534 (15)	0.0420 (14)	0.0343 (13)	−0.0187 (12)	−0.0031 (11)	−0.0031 (10)
C6	0.0527 (15)	0.0400 (14)	0.0340 (13)	−0.0209 (12)	−0.0010 (11)	−0.0029 (10)
C7	0.0497 (15)	0.0437 (15)	0.0412 (14)	−0.0182 (12)	−0.0021 (11)	−0.0033 (11)
C8	0.0508 (16)	0.0484 (16)	0.0445 (15)	−0.0160 (13)	0.0013 (12)	−0.0082 (12)
C9	0.0535 (16)	0.0506 (16)	0.0380 (13)	−0.0184 (13)	0.0008 (11)	−0.0095 (11)
C10	0.0468 (14)	0.0399 (13)	0.0353 (12)	−0.0193 (11)	0.0013 (10)	−0.0029 (10)
C11	0.0493 (14)	0.0393 (14)	0.0338 (12)	−0.0163 (11)	0.0015 (11)	−0.0034 (10)
C12	0.0700 (19)	0.0494 (17)	0.0504 (16)	−0.0285 (15)	−0.0023 (14)	−0.0087 (13)
C13	0.0461 (14)	0.0468 (15)	0.0364 (13)	−0.0177 (12)	−0.0007 (11)	−0.0069 (11)
C14	0.0552 (17)	0.0576 (18)	0.0460 (15)	−0.0259 (14)	0.0021 (12)	−0.0076 (13)
C15	0.0492 (16)	0.0623 (19)	0.0524 (16)	−0.0167 (14)	0.0000 (13)	−0.0163 (14)
N1	0.0514 (13)	0.0425 (12)	0.0396 (12)	−0.0172 (10)	0.0010 (10)	−0.0023 (9)
N2	0.0568 (14)	0.0426 (12)	0.0313 (11)	−0.0172 (10)	−0.0010 (9)	−0.0048 (9)
N3	0.0512 (13)	0.0453 (13)	0.0353 (11)	−0.0179 (10)	0.0004 (9)	−0.0063 (9)
N4	0.0489 (13)	0.0398 (12)	0.0340 (11)	−0.0168 (10)	−0.0026 (9)	−0.0049 (8)
O1	0.0797 (15)	0.0442 (11)	0.0369 (10)	−0.0150 (10)	−0.0094 (9)	−0.0014 (8)
O1S	0.024 (3)	0.217 (5)	0.210 (5)	−0.017 (4)	0.017 (4)	−0.131 (4)
C1S	0.067 (6)	0.095 (7)	0.060 (5)	−0.011 (5)	0.008 (5)	−0.007 (5)
C2S	0.065 (6)	0.080 (7)	0.048 (5)	−0.026 (5)	0.016 (4)	0.009 (5)
C3S	0.022 (5)	0.171 (15)	0.100 (10)	0.006 (8)	−0.011 (6)	−0.017 (10)
C4S	0.024 (3)	0.217 (5)	0.210 (5)	−0.017 (4)	0.017 (4)	−0.131 (4)

Geometric parameters (Å, º) top

C1—N1	1.346 (3)	C12—H12C	0.9800
C1—C2	1.379 (4)	C13—N4	1.450 (3)
C1—H1	0.9500	C13—C15	1.480 (4)
C2—C3	1.387 (4)	C13—C14	1.496 (4)
C2—H2	0.9500	C13—H13	1.0000
C3—C4	1.396 (4)	C14—C15	1.504 (4)
C3—C12	1.501 (4)	C14—H14A	0.9900
C4—C11	1.403 (4)	C14—H14B	0.9900
C4—N2	1.419 (3)	C15—H15A	0.9900
C5—O1	1.232 (3)	C15—H15B	0.9900
C5—N2	1.347 (3)	N2—H2A	0.8800
C5—C6	1.493 (3)	O1S—C4S	1.497 (17)
C6—C7	1.390 (4)	O1S—H1S	0.8200
C6—C10	1.408 (4)	C1S—C2S	1.315 (15)
C7—C8	1.379 (4)	C1S—H11S	0.9600
C7—H7	0.9500	C1S—H12S	0.9600
C8—C9	1.372 (4)	C1S—H13S	0.9600
C8—H8	0.9500	C2S—C3S	1.380 (16)
C9—N3	1.343 (4)	C2S—H21S	0.9700
C9—H9	0.9500	C2S—H22S	0.9700
C10—N3	1.336 (3)	C3S—C4S	1.293 (15)
C10—N4	1.416 (3)	C3S—H31S	0.9700
C11—N1	1.333 (3)	C3S—H32S	0.9700
C11—N4	1.422 (3)	C4S—H41S	0.9700
C12—H12A	0.9800	C4S—H42S	0.9700
C12—H12B	0.9800

N1—C1—C2	122.9 (3)	C13—C14—C15	59.12 (19)
N1—C1—H1	118.5	C13—C14—H14A	117.9
C2—C1—H1	118.5	C15—C14—H14A	117.9
C1—C2—C3	120.3 (3)	C13—C14—H14B	117.9
C1—C2—H2	119.9	C15—C14—H14B	117.9
C3—C2—H2	119.9	H14A—C14—H14B	115.0
C2—C3—C4	117.3 (2)	C13—C15—C14	60.19 (19)
C2—C3—C12	121.2 (2)	C13—C15—H15A	117.8
C4—C3—C12	121.4 (2)	C14—C15—H15A	117.8
C3—C4—C11	118.7 (2)	C13—C15—H15B	117.8
C3—C4—N2	119.2 (2)	C14—C15—H15B	117.8
C11—C4—N2	122.0 (2)	H15A—C15—H15B	114.9
O1—C5—N2	121.4 (2)	C11—N1—C1	117.2 (2)
O1—C5—C6	119.2 (2)	C5—N2—C4	129.0 (2)
N2—C5—C6	119.5 (2)	C5—N2—H2A	115.5
C7—C6—C10	117.9 (2)	C4—N2—H2A	115.5
C7—C6—C5	117.8 (2)	C10—N3—C9	117.1 (2)
C10—C6—C5	123.9 (2)	C10—N4—C11	114.7 (2)
C8—C7—C6	119.6 (3)	C10—N4—C13	116.68 (19)
C8—C7—H7	120.2	C11—N4—C13	115.8 (2)
C6—C7—H7	120.2	C4S—O1S—H1S	108.6
C9—C8—C7	118.0 (3)	C2S—C1S—H11S	113.2
C9—C8—H8	121.0	C2S—C1S—H12S	109.4
C7—C8—H8	121.0	H11S—C1S—H12S	109.5
N3—C9—C8	124.6 (2)	C2S—C1S—H13S	105.8
N3—C9—H9	117.7	H11S—C1S—H13S	109.5
C8—C9—H9	117.7	H12S—C1S—H13S	109.5
N3—C10—C6	122.8 (2)	C1S—C2S—C3S	164.8 (16)
N3—C10—N4	117.1 (2)	C1S—C2S—H21S	98.8
C6—C10—N4	120.1 (2)	C3S—C2S—H21S	95.5
N1—C11—C4	123.5 (2)	C1S—C2S—H22S	92.2
N1—C11—N4	116.4 (2)	C3S—C2S—H22S	89.7
C4—C11—N4	120.1 (2)	H21S—C2S—H22S	103.2
C3—C12—H12A	109.5	C4S—C3S—C2S	152.3 (18)
C3—C12—H12B	109.5	C4S—C3S—H31S	100.9
H12A—C12—H12B	109.5	C2S—C3S—H31S	100.7
C3—C12—H12C	109.5	C4S—C3S—H32S	97.0
H12A—C12—H12C	109.5	C2S—C3S—H32S	94.3
H12B—C12—H12C	109.5	H31S—C3S—H32S	104.1
N4—C13—C15	115.3 (2)	C3S—C4S—O1S	158.0 (19)
N4—C13—C14	116.6 (2)	C3S—C4S—H41S	95.7
C15—C13—C14	60.7 (2)	O1S—C4S—H41S	97.1
N4—C13—H13	117.3	C3S—C4S—H42S	96.0
C15—C13—H13	117.3	O1S—C4S—H42S	98.3
C14—C13—H13	117.3	H41S—C4S—H42S	103.6

N1—C1—C2—C3	−1.8 (4)	C4—C11—N1—C1	1.1 (4)
C1—C2—C3—C4	1.0 (4)	N4—C11—N1—C1	179.3 (2)
C1—C2—C3—C12	−177.4 (3)	C2—C1—N1—C11	0.7 (4)
C2—C3—C4—C11	0.7 (4)	O1—C5—N2—C4	175.9 (3)
C12—C3—C4—C11	179.1 (2)	C6—C5—N2—C4	−2.5 (4)
C2—C3—C4—N2	−174.4 (2)	C3—C4—N2—C5	−141.5 (3)
C12—C3—C4—N2	4.0 (4)	C11—C4—N2—C5	43.5 (4)
O1—C5—C6—C7	−32.6 (4)	C6—C10—N3—C9	−1.6 (4)
N2—C5—C6—C7	145.8 (3)	N4—C10—N3—C9	−179.9 (2)
O1—C5—C6—C10	141.0 (3)	C8—C9—N3—C10	1.1 (4)
N2—C5—C6—C10	−40.5 (4)	N3—C10—N4—C11	−118.4 (2)
C10—C6—C7—C8	1.5 (4)	C6—C10—N4—C11	63.2 (3)
C5—C6—C7—C8	175.6 (2)	N3—C10—N4—C13	21.7 (3)
C6—C7—C8—C9	−1.9 (4)	C6—C10—N4—C13	−156.7 (2)
C7—C8—C9—N3	0.6 (4)	N1—C11—N4—C10	119.0 (2)
C7—C6—C10—N3	0.3 (4)	C4—C11—N4—C10	−62.8 (3)
C5—C6—C10—N3	−173.4 (2)	N1—C11—N4—C13	−21.5 (3)
C7—C6—C10—N4	178.6 (2)	C4—C11—N4—C13	156.7 (2)
C5—C6—C10—N4	4.9 (4)	C15—C13—N4—C10	150.4 (2)
C3—C4—C11—N1	−1.9 (4)	C14—C13—N4—C10	82.0 (3)
N2—C4—C11—N1	173.1 (2)	C15—C13—N4—C11	−70.0 (3)
C3—C4—C11—N4	−179.9 (2)	C14—C13—N4—C11	−138.3 (2)
N2—C4—C11—N4	−4.9 (4)	C1S—C2S—C3S—C4S	41 (7)
N4—C13—C14—C15	105.5 (3)	C2S—C3S—C4S—O1S	−105 (6)
N4—C13—C15—C14	−107.6 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···O1ⁱ	0.88	Missing	2.957 (3)	Missing

Symmetry code: (i) −x, −y, −z.

Experimental details

Crystal data
Chemical formula	C₁₅H₁₄N₄O·0.3C₄H₁₀O
M_r	288.54
Crystal system, space group	Triclinic, P1
Temperature (K)	150
a, b, c (Å)	7.8116 (6), 8.4302 (7), 12.5451 (11)
α, β, γ (°)	84.817 (5), 88.415 (5), 68.252 (4)
V (Å³)	764.18 (11)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.08
Crystal size (mm)	0.47 × 0.29 × 0.07

Data collection
Diffractometer	Nonius KappaCCD area-detector
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	12941, 3141, 2295
R_int	0.100
(sin θ/λ)_max (Å⁻¹)	0.634

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.075, 0.237, 1.08
No. of reflections	3141
No. of parameters	222
No. of restraints	28
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.51, −0.24

Computer programs: COLLECT (Nonius, 2000), SCALEPACK (Otwinowski & Minor, 1997) and DENZO (Otwinowski & Minor, 1997), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), ORTEP-3 for Windows (Farrugia, 1997), WinGX (Farrugia, 1999).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···O1ⁱ	0.88	Missing	2.957 (3)	Missing

Symmetry code: (i) −x, −y, −z.

Acknowledgements

This study was supported by CNPq, CAPES and UNESCO. The authors thanks Maribel Ferro for help in the crystallization process.

References

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