(R)-(+)-2-{[(3-Methyl-4-nitro­pyridin-2-yl)meth­yl]sulfin­yl}-1H-benzimidazole

Naga Raju, M.; Uday Kumar, N.; Kolla, N.; Bandichhor, R.; Vishweshwar, P.

doi:10.1107/S1600536811029990

organic compounds

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ISSN: 2056-9890

Volume 67| Part 8| August 2011| Page o2190

doi:10.1107/S1600536811029990

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(R)-(+)-2-{[(3-Methyl-4-nitropyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole †

Manne Naga Raju,^a Neelam Uday Kumar,^a Naveenkumar Kolla,^a Rakeshwar Bandichhor ^a and Peddy Vishweshwar ^b ^*

^aResearch and Development, API-PDT-03, Integrated Product Development (IPD), Innovation Plaza, Dr Reddy's Laboratories Ltd, Bachupally, Qutubullapur, Hyderabad 500 072, India, and ^bCentre of Excellence in Polymorphism and Particle Engineering, Integrated Product Development (IPD), Innovation Plaza, Dr Reddy's Laboratories Ltd, Bachupally, Qutubullapur, Hyderabad 500 072, India
^*Correspondence e-mail: vishweshwarp@drreddys.com

(Received 23 May 2011; accepted 25 July 2011; online 30 July 2011)

The title compound, C₁₄H₁₂N₄O₃S, is an intermediate of Dexlansoprazole, a proton pump inhibitor (PPI) mainly developed for anti-ulcer activity. The absolute configuration of the title compound was determined as R. The crystal structure reveals that the molecules form chains along the b axis through N—H⋯N and C—H⋯O hydrogen-bonded dimers. These chains are connected via weak C—H⋯O hydrogen bonds.

Related literature

For the synthesis of the title compound, see: Kumar et al. (2009 ). For background to this class of anti-ulcer drugs, see: Arimori et al. (1998 ); Masa et al. (2001 ). For a related structure, see: Fujishima et al. (2002 ).

Experimental

Crystal data

C₁₄H₁₂N₄O₃S
M_r = 316.33
Monoclinic, P 2₁
a = 7.7422 (13) Å
b = 11.0505 (15) Å
c = 8.2318 (13) Å
β = 103.697 (7)°
V = 684.24 (18) Å³
Z = 2
Mo Kα radiation
μ = 0.26 mm⁻¹
T = 298 K
0.22 × 0.20 × 0.18 mm

Data collection

Rigaku Mercury diffractometer
Absorption correction: multi-scan (REQAB; Jacobson, 1998 ) T_min = 0.942, T_max = 0.950
7636 measured reflections
2752 independent reflections
2601 reflections with F² > 2σ(F²)
R_int = 0.025

Refinement

R[F² > 2σ(F²)] = 0.037
wR(F²) = 0.038
S = 1.25
2752 reflections
215 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.48 e Å⁻³
Δρ_min = −0.37 e Å⁻³
Absolute structure: Flack (1983 ), with 1292 Friedel pairs
Flack parameter: −0.02 (4)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯N2ⁱ	0.881 (17)	2.553 (18)	3.425 (2)	170.5 (13)
C2—H2⋯O1ⁱⁱ	0.95	2.33	3.251 (2)	164
C12—H12⋯O2ⁱⁱⁱ	0.95	2.55	3.164 (2)	122
Symmetry codes: (i) $[-x+1, y+{\script{1\over 2}}, -z+1]$ ; (ii) $[-x+1, y-{\script{1\over 2}}, -z+1]$ ; (iii) $[-x-1, y+{\script{1\over 2}}, -z]$ .

Data collection: CrystalClear (Rigaku, 2005 ); cell refinement: CrystalClear; data reduction: CrystalStructure (Molecular Structure Corporation & Rigaku, 2006 ); program(s) used to solve structure: SIR2004 (Burla et al. 2005 ); program(s) used to refine structure: CRYSTALS (Betteridge et al. 2003 ); molecular graphics: X-SEED (Barbour, 2001 ); software used to prepare material for publication: CrystalStructure.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811029990/gw2104sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536811029990/gw2104Isup3.hkl

Supporting information file. DOI: 10.1107/S1600536811029990/gw2104Isup3.cml

checkCIF report

Comment top

Dexlansoprazole II ((R)-(+)) (Fig. 1), (R)-enantiomer of Lansoprazole, is a proton pump inhibitor (PPI) mainly developed for anti-ulcer activity by TAP Pharmaceuticals Ltd., employing new modified-release technology (Arimori et al. 1998; Masa et al. 2001). Dexlansoprazole II ((R)-(+)) was first approved by United States Food and Drug Administration (US-FDA) in the form of 30 and 60 mg capsules for the management of patients with erosive oesophagitis and non-erosive reflux disease (GERD or GORD), under the brand name of DEXILANT.

An alternative and large-scale synthetic method for II ((R)-(+)) was developed in our laboratory by employing asymmetric oxidation conditions on prochiral nitrosulfide intermediate to yield enantiomerically enriched nitro sulphoxide derivative of the title compound I ((R)-(+)) as first stage intermediate (>90% ee) (Kumar et al. 2009). Titanium derived chiral complex (2.2:1.1:0.6 ratio of Titanium (IV)-i-propoxide:(+)-Diethyl L-tartrate:Water) was used in the reaction to induce the chirality. The enantiomerically enriched title compound I ((R)-(+)) as a resultant was subjected to acetone mediated crystallization to yield enantiopure I ((R)-(+)) (>97% ee) which on treatment with potassium salt of 2,2,2-triflouroethanol in dimethylformamide (DMF) yielded Dexlansoprazole II ((R)-(+)) with ICH quality having >99.8% ee.

The structure and stereochemistry of Dexlansoprazole II ((R)-(+)) was well established in the literature with various spectroscopic and single-crystal X-ray diffraction (Fujishima et al. 2002). Herein we have determined the absolute configuration of the title compound I as `R' by anomalous dispersion (Fig. 2). The Flack parameter value, -0.02 (4) for the assigned absolute configuration, suggest that it is correct with high accuracy. The title compound is enantipure sulphoxide containing substituents of benzimidazole and 2-(3-methyl-4-nitro-pyridin-2-yl) methane moieties with dextro (d)- optical configuration. The crystal structure reveals that title molecules are forming chains along the b axis through N₁—H···N₂ and C₂—H···O₁ hydrogen-bonded dimers. Such chains are connected via weak C₁₂—H···O₂ hydrogen bonds (Fig. 3).

Related literature top

For the synthesis of the title compound, see: Kumar et al. (2009). For background to this class of anti-ulcer drugs, see: Arimori et al. (1998); Masa et al. (2001). For a related structure, see: Fujishima et al. (2002). [Please check added text]

Experimental top

A mixture of enantiomerically enriched title compound I ((R)-(+)) (12 g, 0.038 mol) and acetone (264 ml) were heated to 45–50 °C until clear solution obtained. The resulting clear solution was cooled to -5 to 0 °C and stirred for 1.0–1.5 h. The precipitated I (RS)-(±) was filtered and the filtrate was evaporated under vacuum at below 45 °C to obtain thick residue of the title compound I ((R)-(+)). The resulting thick residue of the title compound I ((R)-(+)) was dissolved in dichloromethane and kept for slow solvent evaporation to grow single crystals.

Computing details top

Data collection: CrystalClear (Rigaku, 2005); cell refinement: CrystalClear (Rigaku, 2005); data reduction: CrystalStructure (Molecular Structure Corporation & Rigaku, 2006); program(s) used to solve structure: SIR2004 (Burla et al. 2005); program(s) used to refine structure: CRYSTALS (Betteridge et al. 2003); molecular graphics: X-SEED (Barbour, 2001); software used to prepare material for publication: CrystalStructure (Molecular Structure Corporation & Rigaku, 2006).

Figures top

	Fig. 1. Schematic diagram of Dexlansoprazole (II) ((R)-(+)).
	Fig. 2. Molecular structure of (I), showing the atom numbering scheme. The displacement ellipsoids are drawn at the 50% probability level. H atoms are shown by small circles of arbitrary radii.
	Fig. 3. Crystal packing of (I).

(R)-(+)-2-{[(3-Methyl-4-nitropyridin-2-yl)methyl]sulfinyl}- 1H-benzimidazole top

Crystal data top

C₁₄H₁₂N₄O₃S	F(000) = 328.00
M_r = 316.33	D_x = 1.535 Mg m⁻³
Monoclinic, P2₁	Mo Kα radiation, λ = 0.71070 Å
Hall symbol: P 2yb	Cell parameters from 4183 reflections
a = 7.7422 (13) Å	θ = 1.8–27.5°
b = 11.0505 (15) Å	µ = 0.26 mm⁻¹
c = 8.2318 (13) Å	T = 298 K
β = 103.697 (7)°	Prism, colourless
V = 684.24 (18) Å³	0.22 × 0.20 × 0.18 mm
Z = 2

Data collection top

Rigaku Mercury diffractometer	2601 reflections with F² > 2σ(F²)
Detector resolution: 7.31 pixels mm^-1	R_int = 0.025
ω scans	θ_max = 27.5°
Absorption correction: multi-scan (REQAB; Jacobson, 1998)	h = −10→10
T_min = 0.942, T_max = 0.950	k = −13→13
7636 measured reflections	l = −7→10
2752 independent reflections

Refinement top

Refinement on F²	w = 1/[σ²(F_o²) + (0.1P)²] where P = (F_o² + 2F_c²)/3
R[F² > 2σ(F²)] = 0.037	(Δ/σ)_max < 0.001
wR(F²) = 0.038	Δρ_max = 0.48 e Å⁻³
S = 1.25	Δρ_min = −0.37 e Å⁻³
2752 reflections	Absolute structure: Flack (1983), with 1292 Friedel pairs
215 parameters	Absolute structure parameter: −0.02 (4)
H atoms treated by a mixture of independent and constrained refinement

Crystal data top

C₁₄H₁₂N₄O₃S	V = 684.24 (18) Å³
M_r = 316.33	Z = 2
Monoclinic, P2₁	Mo Kα radiation
a = 7.7422 (13) Å	µ = 0.26 mm⁻¹
b = 11.0505 (15) Å	T = 298 K
c = 8.2318 (13) Å	0.22 × 0.20 × 0.18 mm
β = 103.697 (7)°

Data collection top

Rigaku Mercury diffractometer	2752 independent reflections
Absorption correction: multi-scan (REQAB; Jacobson, 1998)	2601 reflections with F² > 2σ(F²)
T_min = 0.942, T_max = 0.950	R_int = 0.025
7636 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.037	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.038	Δρ_max = 0.48 e Å⁻³
S = 1.25	Δρ_min = −0.37 e Å⁻³
2752 reflections	Absolute structure: Flack (1983), with 1292 Friedel pairs
215 parameters	Absolute structure parameter: −0.02 (4)

Special details top

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

Refinement. Refinement was performed using all reflections. The weighted R-factor (wR) and goodness of fit (S) are based on F². R-factor (gt) are based on F. The threshold expression of F² > 2.0 σ(F²) is used only for calculating R-factor (gt).

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

	x	y	z	U_iso*/U_eq
S1	0.23549 (4)	0.46611 (4)	0.34638 (4)	0.0355 (1)
O1	0.24188 (14)	0.57292 (10)	0.23887 (14)	0.0447 (3)
O2	−0.55199 (16)	0.35772 (11)	0.11414 (16)	0.0604 (4)
O3	−0.57873 (16)	0.49507 (15)	−0.07757 (16)	0.0692 (5)
N1	0.51652 (18)	0.57978 (12)	0.55851 (18)	0.0374 (4)
N2	0.52568 (17)	0.37538 (12)	0.56996 (17)	0.0364 (4)
N3	−0.10635 (16)	0.66905 (11)	0.35720 (17)	0.0430 (4)
N4	−0.50763 (15)	0.45265 (15)	0.05912 (16)	0.0469 (4)
C1	0.43749 (15)	0.47231 (17)	0.50384 (15)	0.0352 (3)
C2	0.8180 (2)	0.36409 (15)	0.7887 (2)	0.0410 (5)
C3	0.9495 (2)	0.43573 (13)	0.8856 (2)	0.0438 (5)
C4	0.9417 (2)	0.56196 (15)	0.8789 (2)	0.0461 (5)
C5	0.8050 (2)	0.62249 (14)	0.7738 (2)	0.0417 (5)
C6	0.6711 (2)	0.55050 (13)	0.67435 (19)	0.0343 (5)
C7	0.6765 (2)	0.42432 (13)	0.6819 (2)	0.0336 (4)
C8	0.08069 (19)	0.50405 (15)	0.47829 (19)	0.0446 (5)
C9	−0.09062 (19)	0.54887 (13)	0.36425 (19)	0.0371 (4)
C10	−0.21640 (16)	0.46761 (16)	0.27169 (16)	0.0369 (3)
C11	−0.36204 (19)	0.52325 (14)	0.1662 (2)	0.0383 (4)
C12	−0.3806 (2)	0.64707 (13)	0.1538 (2)	0.0434 (5)
C13	−0.2491 (2)	0.71654 (15)	0.2537 (2)	0.0454 (5)
C14	−0.1877 (2)	0.33262 (15)	0.2842 (2)	0.0542 (6)
H1	0.494 (2)	0.6529 (16)	0.516 (2)	0.055 (5)*
H2	0.82390	0.27830	0.79360	0.0480*
H3	1.04750	0.39780	0.95950	0.0500*
H4	1.03430	0.60730	0.94910	0.0530*
H5	0.80050	0.70840	0.76880	0.0490*
H12	−0.48000	0.68360	0.08020	0.0510*
H13	−0.26100	0.80210	0.24930	0.0540*
H81	0.05890	0.43470	0.53870	0.0520*
H82	0.13040	0.56640	0.55450	0.0530*
H141	−0.29960	0.29300	0.26470	0.0660*
H142	−0.12570	0.30650	0.20380	0.0660*
H143	−0.12000	0.31340	0.39320	0.0660*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0266 (1)	0.0382 (2)	0.0387 (2)	0.0014 (2)	0.0019 (1)	−0.0015 (2)
O1	0.0386 (5)	0.0509 (6)	0.0422 (6)	0.0037 (4)	0.0051 (4)	0.0085 (4)
O2	0.0521 (7)	0.0478 (7)	0.0793 (9)	−0.0140 (6)	0.0116 (6)	−0.0158 (6)
O3	0.0467 (6)	0.1104 (13)	0.0441 (6)	−0.0083 (7)	−0.0019 (5)	−0.0079 (7)
N1	0.0350 (7)	0.0330 (6)	0.0412 (7)	0.0040 (5)	0.0029 (6)	0.0029 (6)
N2	0.0302 (6)	0.0355 (6)	0.0401 (7)	−0.0010 (5)	0.0015 (5)	0.0009 (6)
N3	0.0369 (7)	0.0406 (7)	0.0516 (8)	−0.0051 (5)	0.0110 (6)	−0.0030 (5)
N4	0.0320 (6)	0.0581 (9)	0.0502 (7)	−0.0062 (7)	0.0088 (5)	−0.0179 (8)
C1	0.0258 (5)	0.0395 (7)	0.0381 (6)	−0.0008 (7)	0.0030 (4)	−0.0012 (8)
C2	0.0389 (8)	0.0372 (8)	0.0435 (8)	0.0058 (7)	0.0028 (7)	0.0037 (7)
C3	0.0322 (7)	0.0528 (10)	0.0399 (8)	0.0058 (6)	−0.0043 (6)	0.0029 (7)
C4	0.0360 (8)	0.0552 (9)	0.0414 (9)	−0.0054 (7)	−0.0019 (7)	−0.0057 (8)
C5	0.0401 (8)	0.0343 (7)	0.0480 (9)	−0.0037 (6)	0.0053 (7)	−0.0025 (7)
C6	0.0311 (8)	0.0373 (8)	0.0350 (8)	0.0025 (6)	0.0089 (6)	0.0032 (6)
C7	0.0226 (7)	0.0407 (8)	0.0355 (8)	−0.0005 (5)	0.0032 (6)	0.0015 (5)
C8	0.0312 (7)	0.0580 (10)	0.0420 (8)	0.0063 (6)	0.0038 (6)	0.0046 (6)
C9	0.0280 (7)	0.0433 (8)	0.0399 (8)	0.0042 (5)	0.0079 (6)	0.0028 (6)
C10	0.0304 (5)	0.0385 (6)	0.0433 (6)	0.0012 (8)	0.0116 (5)	0.0006 (9)
C11	0.0290 (7)	0.0430 (8)	0.0449 (8)	−0.0024 (5)	0.0126 (7)	−0.0055 (6)
C12	0.0366 (8)	0.0427 (8)	0.0490 (9)	0.0051 (6)	0.0066 (6)	0.0053 (7)
C13	0.0431 (9)	0.0355 (7)	0.0566 (9)	0.0007 (6)	0.0097 (7)	0.0000 (7)
C14	0.0431 (9)	0.0394 (8)	0.0812 (13)	0.0029 (7)	0.0172 (9)	0.0010 (8)

Geometric parameters (Å, º) top

S1—O1	1.4831 (12)	C6—C7	1.396 (2)
S1—C1	1.7806 (13)	C8—C9	1.515 (2)
S1—C8	1.8460 (16)	C9—C10	1.409 (2)
O2—N4	1.224 (2)	C10—C11	1.393 (2)
O3—N4	1.2229 (19)	C10—C14	1.508 (2)
N1—C1	1.363 (2)	C11—C12	1.377 (2)
N1—C6	1.381 (2)	C12—C13	1.380 (2)
N2—C1	1.317 (2)	C2—H2	0.9500
N2—C7	1.413 (2)	C3—H3	0.9500
N3—C9	1.3336 (19)	C4—H4	0.9500
N3—C13	1.333 (2)	C5—H5	0.9500
N4—C11	1.478 (2)	C8—H81	0.9500
N1—H1	0.881 (17)	C8—H82	0.9500
C2—C3	1.384 (2)	C12—H12	0.9500
C2—C7	1.400 (2)	C13—H13	0.9500
C3—C4	1.397 (2)	C14—H141	0.9500
C4—C5	1.372 (2)	C14—H142	0.9500
C5—C6	1.406 (2)	C14—H143	0.9500

O1—S1—C1	104.84 (7)	C9—C10—C14	121.46 (13)
O1—S1—C8	106.76 (7)	N4—C11—C12	115.39 (14)
C1—S1—C8	98.26 (6)	N4—C11—C10	121.95 (14)
C1—N1—C6	105.78 (12)	C10—C11—C12	122.67 (15)
C1—N2—C7	103.05 (12)	C11—C12—C13	117.33 (15)
C9—N3—C13	118.24 (14)	N3—C13—C12	123.01 (15)
O2—N4—O3	124.37 (15)	C3—C2—H2	122.00
O2—N4—C11	118.23 (13)	C7—C2—H2	122.00
O3—N4—C11	117.38 (15)	C2—C3—H3	119.00
C1—N1—H1	129.6 (11)	C4—C3—H3	119.00
C6—N1—H1	123.1 (11)	C3—C4—H4	119.00
N1—C1—N2	115.09 (12)	C5—C4—H4	119.00
S1—C1—N1	121.48 (13)	C4—C5—H5	122.00
S1—C1—N2	123.35 (13)	C6—C5—H5	122.00
C3—C2—C7	116.71 (14)	S1—C8—H81	110.00
C2—C3—C4	121.98 (15)	S1—C8—H82	110.00
C3—C4—C5	122.11 (15)	C9—C8—H81	110.00
C4—C5—C6	116.34 (14)	C9—C8—H82	109.00
C5—C6—C7	121.95 (14)	H81—C8—H82	109.00
N1—C6—C5	131.98 (14)	C11—C12—H12	122.00
N1—C6—C7	106.07 (13)	C13—C12—H12	121.00
C2—C7—C6	120.90 (14)	N3—C13—H13	118.00
N2—C7—C6	110.00 (13)	C12—C13—H13	119.00
N2—C7—C2	129.10 (14)	C10—C14—H141	109.00
S1—C8—C9	107.75 (10)	C10—C14—H142	110.00
N3—C9—C8	114.20 (13)	C10—C14—H143	109.00
N3—C9—C10	124.54 (14)	H141—C14—H142	109.00
C8—C9—C10	121.22 (13)	H141—C14—H143	109.00
C9—C10—C11	114.19 (15)	H142—C14—H143	109.00
C11—C10—C14	124.31 (14)

O1—S1—C1—N1	31.07 (13)	C3—C2—C7—C6	0.4 (2)
O1—S1—C1—N2	−145.56 (12)	C2—C3—C4—C5	−1.2 (3)
C8—S1—C1—N1	−78.80 (12)	C3—C4—C5—C6	0.9 (2)
C8—S1—C1—N2	104.57 (12)	C4—C5—C6—N1	179.22 (16)
O1—S1—C8—C9	51.34 (12)	C4—C5—C6—C7	0.0 (2)
C1—S1—C8—C9	159.64 (11)	N1—C6—C7—N2	0.34 (18)
C6—N1—C1—S1	−177.91 (10)	N1—C6—C7—C2	179.94 (14)
C6—N1—C1—N2	−1.02 (17)	C5—C6—C7—N2	179.71 (14)
C1—N1—C6—C5	−178.93 (16)	C5—C6—C7—C2	−0.7 (2)
C1—N1—C6—C7	0.35 (17)	S1—C8—C9—N3	−99.34 (14)
C7—N2—C1—S1	178.01 (10)	S1—C8—C9—C10	78.74 (15)
C7—N2—C1—N1	1.18 (16)	N3—C9—C10—C11	1.2 (2)
C1—N2—C7—C2	179.54 (16)	N3—C9—C10—C14	178.94 (14)
C1—N2—C7—C6	−0.90 (17)	C8—C9—C10—C11	−176.73 (13)
C13—N3—C9—C8	176.84 (14)	C8—C9—C10—C14	1.1 (2)
C13—N3—C9—C10	−1.2 (2)	C9—C10—C11—N4	179.93 (14)
C9—N3—C13—C12	−0.1 (2)	C9—C10—C11—C12	0.1 (2)
O2—N4—C11—C10	36.3 (2)	C14—C10—C11—N4	2.2 (2)
O2—N4—C11—C12	−143.88 (15)	C14—C10—C11—C12	−177.62 (15)
O3—N4—C11—C10	−145.52 (15)	N4—C11—C12—C13	178.95 (14)
O3—N4—C11—C12	34.3 (2)	C10—C11—C12—C13	−1.2 (2)
C7—C2—C3—C4	0.5 (2)	C11—C12—C13—N3	1.2 (2)
C3—C2—C7—N2	179.93 (17)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···N2ⁱ	0.881 (17)	2.553 (18)	3.425 (2)	170.5 (13)
C2—H2···O1ⁱⁱ	0.95	2.33	3.251 (2)	164
C12—H12···O2ⁱⁱⁱ	0.95	2.55	3.164 (2)	122

Symmetry codes: (i) −x+1, y+1/2, −z+1; (ii) −x+1, y−1/2, −z+1; (iii) −x−1, y+1/2, −z.

Experimental details

Crystal data
Chemical formula	C₁₄H₁₂N₄O₃S
M_r	316.33
Crystal system, space group	Monoclinic, P2₁
Temperature (K)	298
a, b, c (Å)	7.7422 (13), 11.0505 (15), 8.2318 (13)
β (°)	103.697 (7)
V (Å³)	684.24 (18)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.26
Crystal size (mm)	0.22 × 0.20 × 0.18

Data collection
Diffractometer	Rigaku Mercury diffractometer
Absorption correction	Multi-scan (REQAB; Jacobson, 1998)
T_min, T_max	0.942, 0.950
No. of measured, independent and observed [F² > 2σ(F²)] reflections	7636, 2752, 2601
R_int	0.025
(sin θ/λ)_max (Å⁻¹)	0.649

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.037, 0.038, 1.25
No. of reflections	2752
No. of parameters	215
No. of restraints	?
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.48, −0.37
Absolute structure	Flack (1983), with 1292 Friedel pairs
Absolute structure parameter	−0.02 (4)

Computer programs: CrystalClear (Rigaku, 2005), CrystalStructure (Molecular Structure Corporation & Rigaku, 2006), SIR2004 (Burla et al. 2005), CRYSTALS (Betteridge et al. 2003), X-SEED (Barbour, 2001).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···N2ⁱ	0.881 (17)	2.553 (18)	3.425 (2)	170.5 (13)
C2—H2···O1ⁱⁱ	0.9500	2.3300	3.251 (2)	164.00
C12—H12···O2ⁱⁱⁱ	0.9500	2.5500	3.164 (2)	122.00

Symmetry codes: (i) −x+1, y+1/2, −z+1; (ii) −x+1, y−1/2, −z+1; (iii) −x−1, y+1/2, −z.

Footnotes

†DRL-IPD Communication No. IPDO-IPM-00262.

Acknowledgements

The authors are grateful to the management of IPDO-API and Dr Reddy's Laboratories Ltd for encouragement. Many thanks to our colleagues Srinivas Gangula, Naredla Anitha and Baddam Sudhakar Reddy for their support in the overall process development.

References

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