Literature DB >> 21203233

Ethyl 4-(2-bromo-5-fluoro-phen-yl)-6-methyl-1-phenyl-2-thioxo-1,2,3,4-tetra-hydro-pyrimidine-5-carboxyl-ate.

Hoong-Kun Fun, Samuel Robinson Jebas, M Babu, P S Patil, B Kalluraya, S M Dharmaprakash.

Abstract

In the title mol-ecule, C(20)H(18)BrFN(2)O(2)S, the pyrimidine ring adopts a flattened envelope conformation. The halogenated benzene ring is orthogonal to the planar part of the pyrimidine ring [dihedral angle = 89.05 (4)°], while the other phenyl ring is oriented at an angle of 85.14 (5)°. The ethoxy group is disordered over two orientations with site occpancies of ca 0.869 (4) and 0.131 (4). Intra-molecular C-H⋯Br and C-H⋯O hydrogen bonds generate S(5) and S(6) ring motifs. The crystal structure is stabilized by inter-molecular N-H⋯S, C-H⋯F, C-H⋯O and C-H⋯Br hydrogen bonds.

Entities: Chemical Disease Species

Year: 2008 PMID： 21203233 PMCID： PMC2962151 DOI： 10.1107/S1600536808021685

Source DB: PubMed Journal: Acta Crystallogr Sect E Struct Rep Online ISSN： 1600-5368

Related literature

For the biological activity of pyrimidinone derivatives, see: Atwal (1990 ▶); Matsuda & Hirao (1965 ▶); Sadanandam et al. (1992 ▶). For the synthetic procedure, see: Steele et al. (1998 ▶); Manjual et al. (2004 ▶); Kappe (1993 ▶); Wipf & Cunningham (1995 ▶). For bond-length data, see: Allen et al. (1987 ▶). For ring conformations, see: Cremer & Pople (1975 ▶). For graph-set analysis of hydrogen bonding, see: Bernstein et al. (1995 ▶).

Experimental

Crystal data

C20H18BrFN2O2S M = 449.33 Triclinic, a = 10.0455 (1) Å b = 10.2969 (1) Å c = 10.3714 (1) Å α = 64.286 (1)° β = 83.110 (1)° γ = 78.796 (1)° V = 947.36 (2) Å3 Z = 2 Mo Kα radiation μ = 2.31 mm−1 T = 100 (2) K 0.41 × 0.35 × 0.22 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer Absorption correction: multi-scan (SADABS; Bruker, 2005 ▶) T min = 0.451, T max = 0.631 30132 measured reflections 5490 independent reflections 4895 reflections with I > 2σ(I) R int = 0.029

Refinement

R[F 2 > 2σ(F 2)] = 0.031 wR(F 2) = 0.084 S = 1.04 5490 reflections 267 parameters 15 restraints H-atom parameters constrained Δρmax = 1.01 e Å−3 Δρmin = −0.66 e Å−3 Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: APEX2; data reduction: SAINT (Bruker, 2005 ▶); program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2003 ▶). Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808021685/ci2628sup1.cif Structure factors: contains datablocks I. DOI: 10.1107/S1600536808021685/ci2628Isup2.hkl Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C₂₀H₁₈BrFN₂O₂S	Z = 2
M_r = 449.33	F₀₀₀ = 456
Triclinic, P1	D_x = 1.575 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation λ = 0.71073 Å
a = 10.0455 (1) Å	Cell parameters from 9996 reflections
b = 10.2969 (1) Å	θ = 2.2–37.5º
c = 10.3714 (1) Å	µ = 2.31 mm⁻¹
α = 64.286 (1)º	T = 100 (2) K
β = 83.110 (1)º	Block, colourless
γ = 78.796 (1)º	0.41 × 0.35 × 0.22 mm
V = 947.36 (2) Å³

Bruker SMART APEXII CCD area-detector diffractometer	5490 independent reflections
Radiation source: fine-focus sealed tube	4895 reflections with I > 2σ(I)
Monochromator: graphite	R_int = 0.029
T = 100.0(1) K	θ_max = 30.0º
φ and ω scans	θ_min = 2.1º
Absorption correction: multi-scan(SADABS; Bruker, 2005)	h = −14→14
T_min = 0.451, T_max = 0.631	k = −14→14
30132 measured reflections	l = −14→14

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)] = 0.031	H-atom parameters constrained
wR(F²) = 0.084	w = 1/[σ²(F_o²) + (0.0443P)² + 0.6872P] where P = (F_o² + 2F_c²)/3
S = 1.05	(Δ/σ)_max = 0.001
5490 reflections	Δρ_max = 1.01 e Å⁻³
267 parameters	Δρ_min = −0.66 e Å⁻³
15 restraints	Extinction correction: none
Primary atom site location: structure-invariant direct methods

Experimental. The data was collected with the Oxford Cyrosystem Cobra low-temperature attachment.

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.

	x	y	z	U_iso*/U_eq	Occ. (<1)
Br1	0.718042 (18)	0.65172 (2)	−0.42386 (2)	0.02506 (6)
S1	0.96029 (4)	0.37018 (5)	0.22541 (4)	0.01943 (9)
F1	1.01209 (13)	0.03875 (13)	−0.17700 (14)	0.0324 (3)
O1	0.50168 (14)	0.40666 (18)	−0.20152 (16)	0.0313 (3)
N1	0.81604 (15)	0.43472 (17)	0.00399 (15)	0.0196 (3)
H1N1	0.8781	0.4859	−0.0370	0.023*
N2	0.73979 (14)	0.26404 (16)	0.21844 (15)	0.0163 (3)
C1	0.87086 (17)	0.2259 (2)	−0.13630 (19)	0.0209 (3)
H1	0.8684	0.1647	−0.0365	0.025*
C2	0.94486 (18)	0.1774 (2)	−0.2313 (2)	0.0236 (3)
C3	0.95266 (18)	0.2600 (2)	−0.3770 (2)	0.0231 (3)
H3	1.0052	0.2215	−0.4387	0.028*
C4	0.88166 (17)	0.4003 (2)	−0.43062 (19)	0.0204 (3)
H4	0.8841	0.4596	−0.5308	0.024*
C5	0.80672 (16)	0.45529 (19)	−0.33865 (19)	0.0184 (3)
C6	0.79770 (16)	0.37081 (19)	−0.19184 (18)	0.0175 (3)
C7	0.71816 (17)	0.42662 (19)	−0.08487 (18)	0.0176 (3)
H7	0.6680	0.5269	−0.1394	0.021*
C8	0.61745 (16)	0.32950 (19)	0.00875 (19)	0.0182 (3)
C9	0.50415 (18)	0.3362 (2)	−0.0741 (2)	0.0221 (3)
C13	0.63308 (16)	0.24993 (19)	0.15063 (19)	0.0178 (3)
C14	0.83214 (16)	0.35640 (18)	0.14314 (17)	0.0158 (3)
C15	0.73718 (16)	0.19955 (18)	0.37368 (17)	0.0165 (3)
C16	0.81160 (19)	0.0635 (2)	0.4482 (2)	0.0250 (4)
H16	0.8712	0.0153	0.3985	0.030*
C17	0.7980 (2)	−0.0018 (2)	0.5970 (2)	0.0339 (5)
H17	0.8481	−0.0955	0.6498	0.041*
C18	0.7111 (2)	0.0701 (3)	0.6680 (2)	0.0335 (5)
H18	0.7008	0.0245	0.7694	0.040*
C19	0.6396 (2)	0.2069 (3)	0.5931 (2)	0.0290 (4)
H19	0.5817	0.2561	0.6429	0.035*
C20	0.65228 (17)	0.2732 (2)	0.44396 (19)	0.0206 (3)
H20	0.6033	0.3676	0.3914	0.025*
C21	0.5474 (2)	0.1379 (2)	0.2489 (2)	0.0261 (4)
H21A	0.5000	0.1072	0.1922	0.039*
H21B	0.4807	0.1805	0.3027	0.039*
H21C	0.6057	0.0531	0.3159	0.039*
O2	0.40143 (16)	0.26503 (19)	0.00591 (18)	0.0270 (4)	0.869 (4)
C11	0.2885 (2)	0.2674 (3)	−0.0718 (3)	0.0290 (5)	0.869 (4)
H11A	0.2726	0.3622	−0.1566	0.035*	0.869 (4)
H11B	0.2050	0.2570	−0.0093	0.035*	0.869 (4)
C12	0.3186 (3)	0.1458 (3)	−0.1191 (3)	0.0319 (5)	0.869 (4)
H12A	0.2419	0.1492	−0.1712	0.048*	0.869 (4)
H12B	0.3329	0.0519	−0.0350	0.048*	0.869 (4)
H12C	0.4006	0.1568	−0.1819	0.048*	0.869 (4)
O2A	0.4326 (11)	0.2257 (8)	−0.0408 (13)	0.0270 (4)	0.131 (4)
C11A	0.3310 (13)	0.2655 (15)	−0.1426 (13)	0.018 (3)	0.131 (4)
H11C	0.3703	0.2613	−0.2331	0.021*	0.131 (4)
H11D	0.2784	0.3638	−0.1632	0.021*	0.131 (4)
C12A	0.247 (2)	0.147 (2)	−0.060 (2)	0.047 (5)	0.131 (4)
H12D	0.1690	0.1610	−0.1156	0.071*	0.131 (4)
H12E	0.2146	0.1512	0.0314	0.071*	0.131 (4)
H12F	0.3024	0.0519	−0.0417	0.071*	0.131 (4)

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Br1	0.02414 (10)	0.02346 (10)	0.02129 (10)	0.00017 (6)	0.00032 (6)	−0.00558 (7)
S1	0.02016 (19)	0.0262 (2)	0.01355 (19)	−0.01177 (15)	0.00010 (14)	−0.00673 (16)
F1	0.0345 (6)	0.0264 (6)	0.0341 (7)	0.0048 (5)	−0.0013 (5)	−0.0146 (5)
O1	0.0241 (7)	0.0465 (9)	0.0253 (7)	−0.0044 (6)	−0.0057 (5)	−0.0162 (7)
N1	0.0233 (7)	0.0245 (7)	0.0142 (7)	−0.0131 (6)	0.0005 (5)	−0.0076 (6)
N2	0.0161 (6)	0.0205 (7)	0.0137 (6)	−0.0080 (5)	0.0022 (5)	−0.0072 (5)
C1	0.0198 (8)	0.0302 (9)	0.0189 (8)	−0.0095 (7)	0.0022 (6)	−0.0144 (7)
C2	0.0215 (8)	0.0237 (9)	0.0272 (9)	−0.0014 (6)	−0.0021 (7)	−0.0127 (8)
C3	0.0197 (8)	0.0279 (9)	0.0271 (9)	−0.0068 (7)	0.0052 (6)	−0.0167 (8)
C4	0.0186 (7)	0.0270 (9)	0.0190 (8)	−0.0086 (6)	0.0022 (6)	−0.0116 (7)
C5	0.0160 (7)	0.0203 (8)	0.0194 (8)	−0.0038 (6)	−0.0017 (6)	−0.0083 (7)
C6	0.0155 (7)	0.0232 (8)	0.0177 (8)	−0.0049 (6)	−0.0016 (5)	−0.0111 (7)
C7	0.0185 (7)	0.0219 (8)	0.0145 (7)	−0.0044 (6)	−0.0018 (5)	−0.0090 (6)
C8	0.0160 (7)	0.0229 (8)	0.0204 (8)	−0.0053 (6)	0.0006 (6)	−0.0130 (7)
C9	0.0187 (8)	0.0247 (9)	0.0289 (9)	−0.0017 (6)	−0.0039 (6)	−0.0167 (8)
C13	0.0155 (7)	0.0221 (8)	0.0205 (8)	−0.0068 (6)	0.0028 (6)	−0.0127 (7)
C14	0.0171 (7)	0.0176 (7)	0.0146 (7)	−0.0062 (6)	0.0020 (5)	−0.0077 (6)
C15	0.0163 (7)	0.0185 (7)	0.0140 (7)	−0.0073 (6)	0.0011 (5)	−0.0046 (6)
C16	0.0263 (9)	0.0183 (8)	0.0283 (10)	−0.0045 (7)	−0.0025 (7)	−0.0070 (7)
C17	0.0405 (11)	0.0222 (9)	0.0298 (11)	−0.0139 (8)	−0.0113 (9)	0.0036 (8)
C18	0.0395 (11)	0.0444 (12)	0.0150 (9)	−0.0294 (10)	0.0002 (7)	−0.0021 (8)
C19	0.0257 (9)	0.0476 (12)	0.0210 (9)	−0.0191 (8)	0.0087 (7)	−0.0181 (9)
C20	0.0169 (7)	0.0270 (9)	0.0192 (8)	−0.0065 (6)	0.0025 (6)	−0.0107 (7)
C21	0.0262 (9)	0.0348 (10)	0.0230 (9)	−0.0188 (8)	0.0058 (7)	−0.0134 (8)
O2	0.0213 (7)	0.0337 (9)	0.0305 (9)	−0.0104 (6)	−0.0044 (6)	−0.0144 (7)
C11	0.0200 (10)	0.0367 (13)	0.0351 (14)	−0.0058 (9)	−0.0053 (9)	−0.0179 (11)
C12	0.0316 (12)	0.0354 (13)	0.0353 (13)	−0.0111 (10)	−0.0007 (10)	−0.0187 (11)
O2A	0.0213 (7)	0.0337 (9)	0.0305 (9)	−0.0104 (6)	−0.0044 (6)	−0.0144 (7)
C11A	0.016 (5)	0.032 (6)	0.006 (5)	−0.007 (4)	−0.003 (4)	−0.007 (4)
C12A	0.037 (8)	0.059 (9)	0.038 (8)	−0.026 (7)	−0.014 (6)	−0.003 (6)

Br1—C5	1.8982 (17)	C15—C20	1.383 (2)
S1—C14	1.6867 (16)	C16—C17	1.392 (3)
F1—C2	1.353 (2)	C16—H16	0.95
O1—C9	1.201 (2)	C17—C18	1.386 (4)
N1—C14	1.325 (2)	C17—H17	0.95
N1—C7	1.463 (2)	C18—C19	1.377 (3)
N1—H1N1	0.85	C18—H18	0.95
N2—C14	1.378 (2)	C19—C20	1.394 (3)
N2—C13	1.412 (2)	C19—H19	0.95
N2—C15	1.450 (2)	C20—H20	0.95
C1—C2	1.371 (2)	C21—H21A	0.98
C1—C6	1.424 (3)	C21—H21B	0.98
C1—H1	0.95	C21—H21C	0.98
C2—C3	1.377 (3)	O2—C11	1.459 (3)
C3—C4	1.380 (3)	C11—C12	1.499 (3)
C3—H3	0.95	C11—H11A	0.99
C4—C5	1.388 (2)	C11—H11B	0.99
C4—H4	0.95	C12—H12A	0.98
C5—C6	1.390 (2)	C12—H12B	0.98
C6—C7	1.537 (2)	C12—H12C	0.98
C7—C8	1.510 (2)	O2A—C11A	1.431 (12)
C7—H7	1.00	C11A—C12A	1.501 (15)
C8—C13	1.349 (2)	C11A—H11C	0.99
C8—C9	1.481 (2)	C11A—H11D	0.99
C9—O2A	1.359 (3)	C12A—H12D	0.98
C9—O2	1.361 (2)	C12A—H12E	0.98
C13—C21	1.505 (2)	C12A—H12F	0.98
C15—C16	1.382 (2)

C14—N1—C7	127.83 (14)	C15—C16—C17	119.04 (18)
C14—N1—H1N1	113.1	C15—C16—H16	120.5
C7—N1—H1N1	118.5	C17—C16—H16	120.5
C14—N2—C13	121.82 (14)	C18—C17—C16	119.8 (2)
C14—N2—C15	118.93 (13)	C18—C17—H17	120.1
C13—N2—C15	118.34 (13)	C16—C17—H17	120.1
C2—C1—C6	117.93 (17)	C19—C18—C17	120.74 (18)
C2—C1—H1	121.0	C19—C18—H18	119.6
C6—C1—H1	121.0	C17—C18—H18	119.6
F1—C2—C1	117.18 (17)	C18—C19—C20	119.90 (19)
F1—C2—C3	118.70 (16)	C18—C19—H19	120.1
C1—C2—C3	124.11 (18)	C20—C19—H19	120.1
C2—C3—C4	117.87 (16)	C15—C20—C19	119.04 (18)
C2—C3—H3	121.1	C15—C20—H20	120.5
C4—C3—H3	121.1	C19—C20—H20	120.5
C3—C4—C5	120.24 (17)	C13—C21—H21A	109.5
C3—C4—H4	119.9	C13—C21—H21B	109.5
C5—C4—H4	119.9	H21A—C21—H21B	109.5
C4—C5—C6	121.62 (16)	C13—C21—H21C	109.5
C4—C5—Br1	116.51 (13)	H21A—C21—H21C	109.5
C6—C5—Br1	121.87 (13)	H21B—C21—H21C	109.5
C5—C6—C1	118.20 (15)	C9—O2—C11	116.68 (18)
C5—C6—C7	123.85 (15)	O2—C11—C12	110.62 (19)
C1—C6—C7	117.90 (15)	O2—C11—H11A	109.5
N1—C7—C8	109.92 (14)	C12—C11—H11A	109.5
N1—C7—C6	107.99 (13)	O2—C11—H11B	109.5
C8—C7—C6	112.44 (13)	C12—C11—H11B	109.5
N1—C7—H7	108.8	H11A—C11—H11B	108.1
C8—C7—H7	108.8	C11—C12—H12A	109.5
C6—C7—H7	108.8	C11—C12—H12B	109.5
C13—C8—C9	126.36 (16)	H12A—C12—H12B	109.5
C13—C8—C7	121.87 (14)	C11—C12—H12C	109.5
C9—C8—C7	111.77 (15)	H12A—C12—H12C	109.5
O1—C9—O2A	107.4 (5)	H12B—C12—H12C	109.5
O1—C9—O2	123.54 (17)	C9—O2A—C11A	111.1 (8)
O1—C9—C8	121.38 (17)	O2A—C11A—C12A	99.2 (10)
O2A—C9—C8	124.7 (5)	O2A—C11A—H11C	111.9
O2—C9—C8	114.94 (16)	C12A—C11A—H11C	111.9
C8—C13—N2	120.36 (15)	O2A—C11A—H11D	111.9
C8—C13—C21	125.54 (15)	C12A—C11A—H11D	111.9
N2—C13—C21	114.07 (15)	H11C—C11A—H11D	109.6
N1—C14—N2	117.58 (14)	C11A—C12A—H12D	109.5
N1—C14—S1	121.21 (12)	C11A—C12A—H12E	109.5
N2—C14—S1	121.21 (12)	H12D—C12A—H12E	109.5
C16—C15—C20	121.44 (16)	C11A—C12A—H12F	109.5
C16—C15—N2	120.12 (15)	H12D—C12A—H12F	109.5
C20—C15—N2	118.31 (15)	H12E—C12A—H12F	109.5

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N1···S1ⁱ	0.85	2.51	3.327 (2)	162
C1—H1···F1ⁱⁱ	0.95	2.52	3.370 (2)	148
C7—H7···Br1	1.00	2.69	3.265 (2)	117
C20—H20···O1ⁱⁱⁱ	0.95	2.44	3.368 (3)	164
C21—H21A···O2	0.98	2.11	2.737 (3)	120
C21—H21B···Br1ⁱⁱⁱ	0.98	2.91	3.886 (2)	171

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1N1⋯S1ⁱ	0.85	2.51	3.327 (2)	162
C1—H1⋯F1ⁱⁱ	0.95	2.52	3.370 (2)	148
C7—H7⋯Br1	1.00	2.69	3.265 (2)	117
C20—H20⋯O1ⁱⁱⁱ	0.95	2.44	3.368 (3)	164
C21—H21A⋯O2	0.98	2.11	2.737 (3)	120
C21—H21B⋯Br1ⁱⁱⁱ	0.98	2.91	3.886 (2)	171

Symmetry codes: (i) ; (ii) ; (iii) , .

2 in total

1. A short history of SHELX.

Authors: George M Sheldrick
Journal: Acta Crystallogr A Date: 2007-12-21 Impact factor: 2.290

2. Dihydropyrimidine calcium channel blockers: 2-heterosubstituted 4-aryl-1,4-dihydro-6-methyl-5-pyrimidinecarboxylic acid esters as potent mimics of dihydropyridines.

Authors: K S Atwal; G C Rovnyak; J Schwartz; S Moreland; A Hedberg; J Z Gougoutas; M F Malley; D M Floyd
Journal: J Med Chem Date: 1990-05 Impact factor: 7.446

2 in total