Capecitabine from X-ray powder synchrotron data.

In the title compound [systematic name 5-de-oxy-5-fluoro-N-(pent-yloxycarbon-yl)cytidine], C(15)H(22)FN(3)O(6), the pentyl chain is disordered over two positions with refined occupancies of 0.53 (5) and 0.47 (5). The furan ring assumes an envelope conformation. In the crystal, inter-molecular N-H⋯O hydrogen bonds link the mol-ecules into chains propagating along the b axis. The crystal packing exhibits electrostatic inter-actions between the 5-fluoro-pyrimidin-2(1H)-one fragments of neighbouring mol-ecules as indicated by short O⋯C [2.875 (3) and 2.961 (3) Å] and F⋯C [2.886 (3) Å] contacts.

Related literature

Capecitabine is the first FDA-approved oral chemotherapy for the treatment for some types of cancer, including advanced bowel cancer or breast cancer, see: Wagstaff et al. (2003 ▶); Jones et al. (2004 ▶).

Experimental

Crystal data

C15H22FN3O6

M = 359.35

Orthorhombic,

a = 5.20527 (2) Å

b = 9.52235 (4) Å

c = 34.77985 (13) Å

V = 1723.91 (1) Å3

Z = 4

Synchrotron radiation

λ = 0.79483 (4) Å

μ = 0.15 mm−1

T = 293 K

Specimen shape: cylinder

40 × 1 × 1 mm

Specimen prepared at 101 kPa

Specimen prepared at 293 K

Particle morphology: no specific habit, white

Data collection

ID31 ESRF Grenoble diffractometer

Specimen mounting: 1.0 mm borosilicate glass capillary

Specimen mounted in transmission mode

Scan method: step

Absorption correction: none

2θmin = 1.0, 2θmax = 35.0°

Increment in 2θ = 0.003°

Refinement

R p = 0.055

R wp = 0.074

R exp = 0.036

R B = 0.102

S = 2.11

Wavelength of incident radiation: 0.79483(4) Å

Excluded region(s): no

Profile function: Pseudo-Voigt profile coefficients as parameterized in Thompson et al. (1987 ▶), asymmetry correction according to Finger et al. (1994 ▶)

499 reflections

91 parameters

77 restraints

H-atom parameters not refined

Preferred orientation correction: March–Dollase (Dollase, 1986 ▶); direction of preferred orientation 001, texture parameter r = 1.03 (1)

Data collection: ESRF SPEC package; cell refinement: GSAS (Larson & Von Dreele, 1994 ▶); data reduction: CRYSFIRE2004 (Shirley, 2000 ▶) and MOPAC (Dewar et al., 1985 ▶); program(s) used to solve structure: FOX (Favre-Nicolin & Černý, 2002 ▶); program(s) used to refine structure: GSAS; molecular graphics: Mercury (Macrae et al., 2006 ▶) and PLATON (Spek, 2009 ▶); software used to prepare material for publication: enCIFer (Allen et al., 2004 ▶).

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809017905/cv2544sup1.cif

Rietveld powder data: contains datablocks I. DOI: 10.1107/S1600536809017905/cv2544Isup2.rtv

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

C15H22FN3O6	Dx = 1.385 Mg m−3
Mr = 359.35	Synchrotron radiation, λ = 0.79483(4) Å
Orthorhombic, P212121	µ = 0.14 mm−1
a = 5.20527 (2) Å	T = 293 K
b = 9.52235 (4) Å	Particle morphology: no specific habit
c = 34.77985 (13) Å	white
V = 1723.91 (1) Å3	cylinder, 40 × 1 mm
Z = 4	Specimen preparation: Prepared at 293 K and 101 kPa
F(000) = 760

ID31 ESRF Grenoble diffractometer	Data collection mode: transmission
Radiation source: X-Ray	Scan method: step
Si(111)	2θmin = 1.00°, 2θmax = 35.00°, 2θstep = 0.003°
Specimen mounting: 1.0 mm borosilicate glass capillary

Least-squares matrix: full	91 parameters
Rp = 0.055	77 restraints
Rwp = 0.074	6 constraints
Rexp = 0.036	H-atom parameters not refined
RBragg = 0.102	Weighting scheme based on measured s.u.'s w = 1/σ(Yobs)2
χ2 = 4.452	(Δ/σ)max = 0.05
11333 data points	Background function: Shifted Chebyschev
Excluded region(s): no	Preferred orientation correction: March–Dollase (Dollase, 1986); direction of preferred orientation 001, texture parameter r = 1.03(1)
Profile function: Pseudo-Voigt profile coefficients as parameterized in Thompson et al. (1987), asymmetry correction according to Finger et al. (1994)

	x	y	z	Uiso*/Ueq	Occ. (<1)
C1	−0.0205 (8)	0.8964 (3)	0.86415 (10)	0.087 (5)*
C2	0.0063 (7)	0.7423 (4)	0.87424 (8)	0.048 (5)*
C3	0.0924 (6)	0.6753 (3)	0.83655 (8)	0.049 (4)*
C4	−0.0166 (5)	0.7766 (2)	0.80775 (7)	0.081 (5)*
O5	−0.0717 (9)	0.9090 (3)	0.82416 (10)	0.093 (3)*
C6	0.2118 (13)	0.9888 (6)	0.87530 (18)	0.079 (4)*
O7	−0.2355 (9)	0.6775 (5)	0.88107 (14)	0.088 (3)*
O8	0.0594 (11)	0.5279 (3)	0.83793 (13)	0.109 (3)*
N9	0.1175 (4)	0.79531 (18)	0.77283 (7)	0.036 (4)*
C10	0.0276 (4)	0.73076 (17)	0.73805 (7)	0.030 (4)*
C11	0.3307 (5)	0.87392 (18)	0.77201 (7)	0.023 (4)*
C12	0.4772 (3)	0.90315 (14)	0.73950 (6)	0.031 (4)*
C13	0.3691 (3)	0.83732 (13)	0.70512 (6)	0.010 (4)*
N14	0.1675 (4)	0.75150 (16)	0.70410 (6)	0.028 (4)*
O15	−0.1690 (5)	0.6596 (2)	0.73930 (11)	0.046 (3)*
F16	0.6861 (5)	0.98180 (17)	0.74183 (10)	0.072 (2)*
N17	0.4922 (3)	0.86898 (14)	0.67035 (6)	0.030 (3)*
C18	0.4009 (4)	0.8094 (2)	0.63692 (7)	0.063 (5)*
O19	0.2448 (4)	0.7158 (3)	0.63482 (12)	0.108 (3)*
O20	0.5359 (5)	0.8859 (3)	0.60977 (10)	0.087 (4)*
C21	0.491 (4)	0.8346 (15)	0.57240 (14)	0.146 (6)*	0.53 (5)
C22	0.524 (3)	0.957 (2)	0.5449 (2)	0.169 (8)*	0.53 (5)
C23	0.801 (3)	0.9940 (19)	0.5361 (5)	0.174 (9)*	0.53 (5)
C24	0.817 (4)	1.1183 (13)	0.5087 (4)	0.174 (10)*	0.53 (5)
C25	0.700 (5)	1.082 (2)	0.4695 (5)	0.143 (9)*	0.53 (5)
C21a	0.518 (5)	0.8251 (19)	0.57299 (18)	0.146 (6)*	0.47 (5)
C22a	0.680 (3)	0.9142 (19)	0.54603 (17)	0.169 (8)*	0.47 (5)
C23a	0.560 (3)	0.939 (2)	0.5068 (4)	0.174 (9)*	0.47 (5)
C24a	0.764 (5)	0.9452 (15)	0.4756 (2)	0.174 (10)*	0.47 (5)
C25a	0.925 (4)	1.079 (2)	0.4786 (7)	0.143 (9)*	0.47 (5)
H251	0.7123	1.1617	0.453	0.25*	0.53 (5)
H252	0.5245	1.0576	0.4727	0.25*	0.53 (5)
H253	0.7906	1.0057	0.4585	0.25*	0.53 (5)
H241	0.7261	1.1953	0.5195	0.25*	0.53 (5)
H242	0.9921	1.1435	0.5053	0.25*	0.53 (5)
H231	0.8866	1.0173	0.5594	0.25*	0.53 (5)
H232	0.8831	0.9152	0.5246	0.25*	0.53 (5)
H221	0.4433	1.0371	0.5559	0.25*	0.53 (5)
H222	0.4406	0.9338	0.5214	0.25*	0.53 (5)
H211	0.3216	0.7981	0.5706	0.25*	0.53 (5)
H212	0.6111	0.7627	0.5664	0.25*	0.53 (5)
H61	0.1794	1.0833	0.868	0.1*
H62	0.2378	0.9842	0.9023	0.1*
H63	0.361	0.9557	0.8624	0.1*
H21	0.1249	0.7267	0.8946	0.075*
H31	0.273	0.6894	0.8356	0.075*
H11	−0.166	0.9315	0.8775	0.12*
H41	−0.1786	0.7386	0.8007	0.12*
H111	0.3869	0.9132	0.7957	0.03*
H171	0.6224	0.9246	0.6699	0.04*
H82	−0.0753	0.5066	0.8272	0.1*
H72	−0.216	0.592	0.883	0.12*
H2511	1.0505	1.0802	0.4588	0.25*	0.47 (5)
H2512	1.008	1.082	0.5029	0.25*	0.47 (5)
H2513	0.8164	1.1589	0.476	0.25*	0.47 (5)
H2411	0.874	0.8661	0.478	0.25*	0.47 (5)
H2412	0.6824	0.943	0.4511	0.25*	0.47 (5)
H2311	0.4682	1.0252	0.5072	0.25*	0.47 (5)
H2312	0.4442	0.8643	0.5013	0.25*	0.47 (5)
H2211	0.7075	1.0029	0.5578	0.25*	0.47 (5)
H2212	0.8402	0.8684	0.5424	0.25*	0.47 (5)
H2111	0.5817	0.7316	0.5736	0.25*	0.47 (5)
H2112	0.3442	0.8245	0.5647	0.25*	0.47 (5)

C1—C2	1.515 (5)	O20—C21	1.4080 (21)
C1—O5	1.421 (5)	O20—C21a	1.4073 (21)
C1—C6	1.545 (7)	C21—C22	1.5177 (21)
C1—H11	0.950	C21—H211	0.949 (16)
C2—C3	1.525 (4)	C21—H212	0.951 (24)
C2—O7	1.422 (6)	C22—C23	1.5196 (21)
C2—H21	0.950	C22—H221	0.950 (22)
C3—C4	1.502 (4)	C22—H222	0.950 (9)
C3—O8	1.413 (4)	C23—C24	1.5219 (21)
C3—H31	0.950	C23—H231	0.950 (19)
C4—O5	1.413 (4)	C23—H232	0.951 (22)
C4—N9	1.4123 (19)	C24—H241	0.949 (19)
C4—H41	0.950	C24—H242	0.951 (20)
C6—H61	0.950	C25—C24	1.5304 (21)
C6—H62	0.950	C25—H251	0.951 (19)
C6—H63	0.950	C25—H252	0.952 (26)
O7—H72	0.820	C25—H253	0.950 (23)
O8—H82	0.820	C21a—C22a	1.5189 (21)
N9—C10	1.4352 (18)	C21a—H2111	0.950 (25)
N9—C11	1.3389 (19)	C21a—H2112	0.951 (26)
C10—N14	1.4015 (19)	C22a—C23a	1.5195 (21)
C10—O15	1.2282 (19)	C22a—H2211	0.950 (15)
C11—C12	1.3919 (19)	C22a—H2212	0.950 (21)
C11—H111	0.950	C23a—C24a	1.5233 (21)
C12—C13	1.4625 (19)	C23a—H2311	0.950 (20)
C12—F16	1.3228 (19)	C23a—H2312	0.950 (18)
C13—N14	1.3305 (18)	C24a—C25a	1.5298 (21)
C13—N17	1.4013 (19)	C24a—H2411	0.949 (21)
N17—C18	1.3783 (19)	C24a—H2412	0.952 (18)
N17—H171	0.860	C25a—H2511	0.950 (19)
C18—O19	1.2084 (20)	C25a—H2512	0.950 (27)
C18—O20	1.3839 (20)	C25a—H2513	0.950 (26)
O15···C12i	2.961 (3)	O15···C11iii	2.875 (3)
F16···C10ii	2.886 (3)
C2—C1—O5	109.0 (3)	O20—C21—H212	110.1 (17)
C2—C1—C6	114.90 (20)	C22—C21—H211	110.1 (16)
C2—C1—H11	107.52	C22—C21—H212	109.9 (6)
O5—C1—C6	110.16 (20)	H211—C21—H212	109.4 (9)
O5—C1—H11	107.4	C21—C22—C23	114.26 (21)
C6—C1—H11	107.5	C21—C22—H221	108.2 (6)
C1—C2—C3	103.46 (14)	C21—C22—H222	108.2 (14)
C1—C2—O7	112.16 (19)	C23—C22—H221	108.3 (14)
C1—C2—H21	112.53	C23—C22—H222	108.3 (12)
C3—C2—O7	102.85 (18)	H221—C22—H222	109.5 (16)
C3—C2—H21	112.59	C22—C23—C24	110.85 (21)
O7—C2—H21	112.5	C22—C23—H231	109.1 (13)
C2—C3—C4	101.19 (13)	C22—C23—H232	109.1 (15)
C2—C3—O8	110.48 (18)	C24—C23—H231	109.1 (15)
C2—C3—H31	105.17	C24—C23—H232	109.1 (12)
C4—C3—O8	127.86 (19)	H231—C23—H232	109.5 (16)
C4—C3—H31	105.07	C23—C24—C25	111.26 (21)
O8—C3—H31	105.13	C23—C24—H241	109.1 (12)
C3—C4—O5	112.34 (14)	C23—C24—H242	109.0 (16)
C3—C4—N9	117.90 (12)	C25—C24—H241	109.1 (24)
C3—C4—H41	105.26	C25—C24—H242	109.0 (17)
O5—C4—N9	109.57 (17)	H241—C24—H242	109.4 (11)
O5—C4—H41	105.29	C24—C25—H251	109.6 (20)
N9—C4—H41	105.37	C24—C25—H252	109.5 (21)
C1—O5—C4	106.4 (3)	C24—C25—H253	109.6 (17)
C1—C6—H61	109.5	H251—C25—H252	109.3 (19)
C1—C6—H62	109.5	H251—C25—H253	109.5 (22)
C1—C6—H63	109.4	H252—C25—H253	109.4 (24)
H61—C6—H62	109.4	O20—C21a—C22a	107.18 (20)
H61—C6—H63	109.4	O20—C21a—H2111	110.1 (16)
H62—C6—H63	109.6	O20—C21a—H2112	109.9 (18)
C2—O7—H72	109.5	C22a—C21a—H2111	110.2 (17)
C3—O8—H82	109.47	C22a—C21a—H2112	110.1 (13)
C4—N9—C10	120.62 (14)	H2111—C21a—H2112	109.4 (6)
C4—N9—C11	119.91 (14)	C21a—C22a—C23a	114.36 (21)
C10—N9—C11	119.47 (12)	C21a—C22a—H2211	108.3 (6)
N9—C10—N14	118.71 (13)	C21a—C22a—H2212	108.2 (15)
N9—C10—O15	118.59 (15)	C23a—C22a—H2211	108.2 (19)
N14—C10—O15	122.71 (15)	C23a—C22a—H2212	108.3 (10)
N9—C11—C12	125.65 (14)	H2211—C22a—H2212	109.4 (10)
N9—C11—H111	117.16	C22a—C23a—C24a	110.99 (21)
C12—C11—H111	117.19	C22a—C23a—H2311	109.1 (20)
C11—C12—C13	111.59 (12)	C22a—C23a—H2312	109.0 (11)
C11—C12—F16	120.89 (15)	C24a—C23a—H2311	109.1 (12)
C13—C12—F16	127.52 (14)	C24a—C23a—H2312	109.2 (19)
C12—C13—N14	126.04 (12)	H2311—C23a—H2312	109.5 (16)
C12—C13—N17	115.94 (14)	C23a—C24a—C25a	111.43 (21)
N14—C13—N17	118.02 (18)	C23a—C24a—H2411	109.0 (10)
C10—N14—C13	118.29 (13)	C23a—C24a—H2412	108.9 (21)
C13—N17—C18	118.81 (13)	C25a—C24a—H2411	109.1 (26)
C13—N17—H171	120.56	C25a—C24a—H2412	109.0 (16)
C18—N17—H171	120.63	H2411—C24a—H2412	109.4 (11)
N17—C18—O19	125.88 (16)	C24a—C25a—H2511	109.5 (21)
N17—C18—O20	100.60 (15)	C24a—C25a—H2512	109.5 (21)
O19—C18—O20	133.52 (16)	C24a—C25a—H2513	109.6 (17)
C18—O20—C21	111.26 (20)	H2511—C25a—H2512	109.4 (21)
C18—O20—C21a	111.74 (20)	H2511—C25a—H2513	109.4 (23)
O20—C21—C22	107.29 (21)	H2512—C25a—H2513	109.5 (24)
O20—C21—H211	110.0 (9)

D—H···A	D—H	H···A	D···A	D—H···A
N17—H171···O8ii	0.860	1.956	2.797 (5)	170

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N17—H171⋯O8i	0.860	1.956	2.797 (5)	170

Symmetry code: (i) .