3-[(4-Amino-5-chloro-2-ethoxy­benz­amido)meth­yl]pyrrolo[2,1-c][1,4]oxazin-5-ium chloride monohydrate

Tai-Feng Tong; Jian Zhao; Lin Cheng; Yi-Hua Zhang

doi:10.1107/S160053680803986X

. 2008 Dec 3;65(Pt 1):o14. doi: 10.1107/S160053680803986X

3-[(4-Amino-5-chloro-2-ethoxybenzamido)methyl]pyrrolo[2,1-c][1,4]oxazin-5-ium chloride monohydrate

Tai-Feng Tong ^a, Jian Zhao ^b, Lin Cheng ^b, Yi-Hua Zhang ^a,^*

PMCID: PMC2967935 PMID: 21581599

Abstract

The title compound, C₁₇H₂₅ClN₃O₃ ⁺·Cl⁻·H₂O, is a monohydrated hydrochloride salt of a new derivative of mosapride, which is a pharmaceutical compound possessing gastrointestinal pro-kinetic activity. The chloride anion accepts hydrogen bonds from the NH group of the pyrrolooxazine fused-ring system and from the amine group, and the water molecules form hydrogen bonds that bridge between the chloride anion and the C=O bond of the amide.

Related literature

For related structures and background information concerning mosapride, see: Kakigami et al. (1998 ▶); Morie et al. (1995 ▶); Omae et al. (2002 ▶); Aoki et al. (2007 ▶).

Experimental

Crystal data

C₁₇H₂₅ClN₃O₃ ⁺·Cl⁻·H₂O
M _r = 408.32
Orthorhombic,
a = 8.0984 (9) Å
b = 11.1594 (13) Å
c = 21.843 (3) Å
V = 1974.0 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.36 mm⁻¹
T = 293 (2) K
0.24 × 0.20 × 0.16 mm

Data collection

Bruker APEX CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2000 ▶) T _min = 0.919, T _max = 0.945
10642 measured reflections
3848 independent reflections
3188 reflections with I > 2σ(I)
R _int = 0.037

Refinement

R[F ² > 2σ(F ²)] = 0.050
wR(F ²) = 0.096
S = 1.06
3848 reflections
261 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.32 e Å⁻³
Δρ_min = −0.22 e Å⁻³
Absolute structure: Flack (1983 ▶), 1631 Friedel pairs
Flack parameter: −0.02 (7)

Data collection: SMART (Bruker, 2000 ▶); cell refinement: SAINT (Bruker, 2000 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S160053680803986X/bi2322sup1.cif

e-65-00o14-sup1.cif^{(19.7KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S160053680803986X/bi2322Isup2.hkl

e-65-00o14-Isup2.hkl^{(188.7KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1A⋯Cl1ⁱ	0.84 (4)	2.66 (4)	3.384 (3)	146 (3)
N1—H1B⋯Cl1ⁱⁱ	0.85 (3)	2.45 (3)	3.281 (3)	169 (3)
N3—H3C⋯Cl1	0.92 (3)	2.18 (3)	3.077 (3)	164 (2)
O1W—H1WA⋯Cl1ⁱⁱⁱ	0.79 (3)	2.62 (3)	3.410 (4)	176 (3)
O1W—H1WB⋯O2	0.88 (4)	1.95 (5)	2.800 (4)	161 (4)

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Acknowledgments

The authors thank the Program for Young Excellent Talents in China Pharmaceutical University for financial support.

supplementary crystallographic information

Comment

Mosapride citrate is a benzamide derivative that possesses a gastrointestinal prokinetic activity (Aoki et al. 2007). The title compound (Fig. 1) is a new mosapride derivative, and crystals of its hydrochloride salt were obtained by acidifying with hydrochloric acid then recrystallizing from methanol.

In the benzamide unit, the C=O bond distance of 1.229 (3) Å is much shorter than the C—O bond distances (1.359 (3)–1.432 (3) Å), showing it to have full double-bond character. Meanwhile, the C9—N2 distance of 1.330 (4) Å is comparable with that of C4—N1 (1.352 (4) Å), but much shorter than N2—C10 (1.441 (3) Å), N3—C13 (1.493 (4) Å), N3—C14 (1.489 (4) Å) and N3—C17 (1.492 (4) Å). Thus, the C4—N1 bond has partial double-bond character.

Experimental

A mixture of 4-amino-5-chloro-2-ethoxybenzoic acid (8.613 g, 40 mmol), (hexahydro-1H-pyrrolo[2,1-c][1,4]oxazin-3-yl)methanamine (4.8 g, 30.72 mmol) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (11.8 g, 61.8 mmol) in CH₂Cl₂ (60 ml) was stirred for two hours under an argon atmosphere. The products were treated with saturated NaHCO₃ (200 ml) and extracted with CH₂Cl₂ (3 × 300 ml), then the organic layer was dried with anhydrous MgSO₄ and distilled under vacuum. The white solids were collected and dried (yield 5.856 g, 54.0%). Crystals of the title compound were obtained by acidifying with hydrochloric acid then recrystallizing from methanol.