7-(4-Bromo­phenyl)-5-cyano­methyl-1,3-di­methyl­pyrido­[2,3-d]­pyrimidine-2,4-dione

Sarkhel, S.; Srivastava, P.; Saxena, A.S.; Ram, V.J.; Prasad, O.; Shiro, M.; Maulik, P.R.

doi:10.1107/S1600536801004986

7-(4-Bromophenyl)-5-cyanomethyl-1,3-dimethylpyrido[2,3-d]pyrimidine-2,4-dione

S. Sarkhel, P. Srivastava, A. S. Saxena, V. J. Ram, O. Prasad, M. Shiro and P. R. Maulik

The positions of the cyanomethyl and 4-bromophenyl substituents in the title compound, C₁₇H₁₃BrN₄O₂, have been confirmed by single-crystal X-ray structure determination. The crystal packing shows weak hydrogen-bonding and aromatic π–π interactions.

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Supporting information

	Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536801004986/bt6027sup1.cif Contains datablocks global, I
	Structure factor file (CIF format) https://doi.org/10.1107/S1600536801004986/bt6027Isup2.hkl Contains datablock I

CCDC reference: 165649

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Key indicators

Single-crystal X-ray study
T = 296 K
Mean (C-C) = 0.007 Å
R factor = 0.043
wR factor = 0.120
Data-to-parameter ratio = 16.5

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No syntax errors found

ADDSYM reports no extra symmetry


 Alert Level C:



ABSTM_02  Alert C The ratio of expected to reported Tmax/Tmin(RR) is > 1.10
          Tmin and Tmax reported:      0.509     0.769
          Tmin and Tmax expected:      0.398     0.769
          RR =      1.277
          Please check that your absorption correction is appropriate.


 0 Alert Level A = Potentially serious problem

 0 Alert Level B = Potential problem

 1 Alert Level C = Please check

Comment top

The therapeutic importance (Furuya & Ohataki, 1994a,b; Heber et al., 1993; Piper et al., 1989) of suitably functionalized pyrido[2,3-d]pyrimidine ring systems enthused us to develop an innovative synthesis in which different substituents could be arranged in a pharmacophoric pattern to display diverse pharmacological activities of higher order. The title compound, (I), was prepared (Srivastava et al., 2000) by ring-transformation reactions of 6-aryl-3-cyano-4-methylthio-2H-pyran-2-one and 6-amino-1,3-dimethyluracil. The present X-ray crystallography study has been undertaken to confirm the structure of (I).

The conformation of (I) along with the atom-numbering scheme is shown in Fig. 1. The molecule contains one fused-ring system (A/B) to which a bromophenyl ring (C) is attached at the 7 position. All the rings are planar [deviations of the atoms from their least-squares planes are within the range -0.015 (3)–0.011 (3) Å]. The bromophenyl ring is coplanar with the A/B ring system [torsion angle N8—C7—C71—C72 - 179.0 (4)°]. The cyano group is twisted out of the A/B plane. The crystal structure analysis reveals the presence of weak hydrogen-bonding interactions, such as C—H···N, C—H···Br and C—H···O (Fig. 2 and Table 1). Moreover, the crystal packing (Fig. 3) also shows intermolecular stacking as a result of π–π interactions between rings B and C (Hunter & Sanders, 1990). The overlapping rings (B and C) are in a `parallel-displaced orientation'; the average distance of separation between their mean planes is 3.480 (6) Å, the angle between them being 1.0 (3)°. The different intermolecular interactions seen in the crystal structure of (I) might well be a reflection of the possible interactions in the molecular recognition process in view of the diverse pharmacological properties associated with the suitably functionalized pyrido[2,3-d]pyrimidines.

Experimental top

The synthesis of (I) was carried out by reaction of 6-amino-1,3-dimethyluracil with 6-(4-bromophenyl)-3-cyano-4-methylthio-2H-pyran-2-one (Srivastava et al., 2000). Diffraction-quality crystals were grown by slow evaporation from a solution in a dichloromethane–ethyl acetate mixture at room temperature.

Computing details top

Data collection: Rigaku/AFC Diffractometer Control Software (Rigaku, 1995); cell refinement: Rigaku/AFC Diffractometer Control Software; data reduction: TEXSAN (Molecular Structure Corporation/Rigaku Corporation, 1998); program(s) used to solve structure: SHELXS86 (Sheldrick, 1990); program(s) used to refine structure: SHELXL93 (Sheldrick, 1993); molecular graphics: NRCVAX (Gabe et al.,, 1989); software used to prepare material for publication: SHELXL93.

Figures top

	Fig. 1. ORTEP (Johnson, 1965) diagram showing the molecular structure of (I) with labelling for non-H atoms and displacement ellipsoids at 50% probability.
	Fig. 2. PLUTO (Motherwell & Clegg, 1978) crystal-packing diagram showing the C—H···O hydrogen bonds as dotted lines and the C—H···Br hydrogen bonds as dashed lines.
	Fig. 3. The crystal packing (perpendicular view to the plane through atoms C6, C7 and N8 of ring B) showing the partial overlapping (as indicated by black shed) of rings B and C owing to intermolecular stacking.

7-(4-bromophenyl)-5-cyanomethyl-1,3-dimethyl-2,4-dioxypyrido[2,3-d]pyrimidine top

Crystal data top

C₁₇H₁₃BrN₄O₂	F(000) = 388
M_r = 385.22	D_x = 1.628 Mg m⁻³
Triclinic, P1	Melting point = 220–230 K
a = 8.728 (3) Å	Mo Kα radiation, λ = 0.71073 Å
b = 12.087 (4) Å	Cell parameters from 24 reflections
c = 8.672 (3) Å	θ = 14.7–15.0°
α = 108.22 (3)°	µ = 2.63 mm⁻¹
β = 113.43 (2)°	T = 296 K
γ = 91.24 (3)°	Block, colourless
V = 786.1 (5) Å³	0.4 × 0.3 × 0.1 mm
Z = 2

Data collection top

Rigaku AFC-5R diffractometer	2254 reflections with I > 2σ(I)
Radiation source: rotating anode	R_int = 0.000
Graphite monochromator	θ_max = 27.5°, θ_min = 2.6°
ω–2θ scans	h = −11→11
Absorption correction: empirical (using intensity measurements) (TEXSAN; Molecular Structure Corporation/Rigaku Corporation, 1998)	k = −15→0
T_min = 0.509, T_max = 0.769	l = −10→11
3619 measured reflections	3 standard reflections every 150 reflections
3619 independent reflections	intensity decay: <0.2%

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.043	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.120	H-atom parameters constrained
S = 1.03	w = 1/[σ²(F_o²) + (0.0669P)² + 0.8316P] where P = (F_o² + 2F_c²)/3
3616 reflections	(Δ/σ)_max < 0.001
219 parameters	Δρ_max = 0.48 e Å⁻³
0 restraints	Δρ_min = −0.43 e Å⁻³

Crystal data top

C₁₇H₁₃BrN₄O₂	γ = 91.24 (3)°
M_r = 385.22	V = 786.1 (5) Å³
Triclinic, P1	Z = 2
a = 8.728 (3) Å	Mo Kα radiation
b = 12.087 (4) Å	µ = 2.63 mm⁻¹
c = 8.672 (3) Å	T = 296 K
α = 108.22 (3)°	0.4 × 0.3 × 0.1 mm
β = 113.43 (2)°

Data collection top

Rigaku AFC-5R diffractometer	2254 reflections with I > 2σ(I)
Absorption correction: empirical (using intensity measurements) (TEXSAN; Molecular Structure Corporation/Rigaku Corporation, 1998)	R_int = 0.000
T_min = 0.509, T_max = 0.769	3 standard reflections every 150 reflections
3619 measured reflections	intensity decay: <0.2%
3619 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.043	0 restraints
wR(F²) = 0.120	H-atom parameters constrained
S = 1.03	Δρ_max = 0.48 e Å⁻³
3616 reflections	Δρ_min = −0.43 e Å⁻³
219 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 on F² for ALL reflections except for 3 with very negative F² or flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses 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
Br	0.08388 (7)	0.28864 (4)	0.14885 (8)	0.0565 (2)
C1A	0.5035 (5)	−0.3069 (3)	−0.0501 (6)	0.0348 (8)
N1	0.4360 (4)	−0.3982 (3)	−0.2164 (5)	0.0402 (8)
C11	0.2806 (6)	−0.3883 (4)	−0.3600 (6)	0.0558 (13)
H11A	0.2939	−0.3130	−0.3726	0.084*
H11B	0.1868	−0.3952	−0.3303	0.084*
H11C	0.2595	−0.4502	−0.4709	0.084*
C2	0.5054 (6)	−0.4975 (4)	−0.2526 (6)	0.0418 (9)
O21	0.4402 (5)	−0.5786 (3)	−0.3964 (5)	0.0631 (10)
N3	0.6523 (5)	−0.5053 (3)	−0.1141 (5)	0.0422 (8)
C31	0.7350 (7)	−0.6072 (4)	−0.1563 (7)	0.0540 (12)
H31A	0.6668	−0.6599	−0.2764	0.081*
H31B	0.7483	−0.6478	−0.0737	0.081*
H31C	0.8443	−0.5809	−0.1463	0.081*
C4	0.7317 (5)	−0.4211 (4)	0.0569 (6)	0.0411 (9)
O41	0.8613 (4)	−0.4372 (3)	0.1683 (5)	0.0575 (9)
C4A	0.6496 (5)	−0.3176 (3)	0.0898 (6)	0.0357 (8)
C5	0.7086 (5)	−0.2240 (4)	0.2554 (6)	0.0387 (9)
C51	0.8651 (6)	−0.2219 (5)	0.4198 (6)	0.0502 (11)
H51A	0.8599	−0.1690	0.5273	0.060*
H51B	0.8668	−0.3004	0.4268	0.060*
C52	1.0196 (7)	−0.1826 (5)	0.4111 (7)	0.0556 (12)
N53	1.1398 (6)	−0.1492 (5)	0.4054 (8)	0.084 (2)
C6	0.6231 (5)	−0.1299 (4)	0.2705 (6)	0.0397 (9)
H6	0.6596	−0.0683	0.3801	0.048*
C7	0.4812 (5)	−0.1261 (3)	0.1220 (6)	0.0352 (8)
C71	0.3874 (5)	−0.0253 (3)	0.1297 (6)	0.0353 (8)
C72	0.4376 (6)	0.0728 (4)	0.2855 (6)	0.0444 (10)
H72	0.5318	0.0754	0.3879	0.053*
C73	0.3483 (6)	0.1675 (4)	0.2903 (6)	0.0467 (10)
H73	0.3838	0.2333	0.3947	0.056*
C74	0.2074 (6)	0.1626 (4)	0.1392 (6)	0.0412 (9)
C75	0.1566 (6)	0.0668 (4)	−0.0179 (6)	0.0449 (10)
H75	0.0623	0.0644	−0.1199	0.054*
C76	0.2483 (6)	−0.0266 (4)	−0.0221 (6)	0.0444 (10)
H76	0.2155	−0.0906	−0.1284	0.053*
N8	0.4227 (4)	−0.2154 (3)	−0.0368 (5)	0.0354 (7)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Br	0.0632 (3)	0.0492 (3)	0.0733 (4)	0.0251 (2)	0.0380 (3)	0.0292 (2)
C1A	0.038 (2)	0.031 (2)	0.037 (2)	0.004 (2)	0.017 (2)	0.012 (2)
N1	0.041 (2)	0.035 (2)	0.037 (2)	0.0084 (15)	0.013 (2)	0.0072 (15)
C11	0.058 (3)	0.052 (3)	0.036 (2)	0.015 (2)	0.008 (2)	0.003 (2)
C2	0.047 (2)	0.036 (2)	0.046 (3)	0.011 (2)	0.024 (2)	0.014 (2)
O21	0.072 (2)	0.042 (2)	0.056 (2)	0.013 (2)	0.021 (2)	−0.001 (2)
N3	0.043 (2)	0.035 (2)	0.054 (2)	0.011 (2)	0.026 (2)	0.016 (2)
C31	0.060 (3)	0.042 (2)	0.070 (3)	0.023 (2)	0.035 (3)	0.022 (2)
C4	0.038 (2)	0.044 (2)	0.050 (3)	0.009 (2)	0.022 (2)	0.022 (2)
O41	0.051 (2)	0.060 (2)	0.063 (2)	0.024 (2)	0.019 (2)	0.029 (2)
C4A	0.034 (2)	0.037 (2)	0.040 (2)	0.009 (2)	0.018 (2)	0.017 (2)
C5	0.038 (2)	0.044 (2)	0.037 (2)	0.008 (2)	0.016 (2)	0.018 (2)
C51	0.049 (3)	0.057 (3)	0.038 (2)	0.010 (2)	0.012 (2)	0.017 (2)
C52	0.044 (3)	0.061 (3)	0.041 (3)	0.009 (2)	0.003 (2)	0.011 (2)
N53	0.041 (3)	0.102 (4)	0.085 (4)	−0.001 (3)	0.012 (3)	0.025 (3)
C6	0.040 (2)	0.038 (2)	0.035 (2)	0.005 (2)	0.015 (2)	0.006 (2)
C7	0.034 (2)	0.034 (2)	0.039 (2)	0.005 (2)	0.018 (2)	0.011 (2)
C71	0.034 (2)	0.034 (2)	0.038 (2)	0.006 (2)	0.016 (2)	0.011 (2)
C72	0.041 (2)	0.041 (2)	0.039 (2)	0.006 (2)	0.013 (2)	0.004 (2)
C73	0.052 (3)	0.037 (2)	0.045 (3)	0.007 (2)	0.021 (2)	0.005 (2)
C74	0.045 (2)	0.039 (2)	0.050 (3)	0.009 (2)	0.027 (2)	0.020 (2)
C75	0.042 (2)	0.048 (2)	0.040 (2)	0.007 (2)	0.012 (2)	0.016 (2)
C76	0.048 (2)	0.042 (2)	0.038 (2)	0.005 (2)	0.016 (2)	0.010 (2)
N8	0.034 (2)	0.034 (2)	0.035 (2)	0.0064 (14)	0.0137 (15)	0.0104 (14)

Geometric parameters (Å, º) top

Br—C74	1.885 (4)	C5—C6	1.374 (6)
C1A—N8	1.323 (5)	C5—C51	1.525 (6)
C1A—N1	1.395 (5)	C51—C52	1.458 (7)
C1A—C4A	1.411 (6)	C52—N53	1.140 (7)
N1—C2	1.361 (5)	C6—C7	1.402 (6)
N1—C11	1.470 (6)	C7—N8	1.345 (5)
C2—O21	1.220 (5)	C7—C71	1.481 (5)
C2—N3	1.395 (6)	C71—C76	1.387 (6)
N3—C4	1.387 (6)	C71—C72	1.388 (6)
N3—C31	1.463 (5)	C72—C73	1.398 (6)
C4—O41	1.228 (5)	C73—C74	1.379 (7)
C4—C4A	1.462 (6)	C74—C75	1.380 (6)
C4A—C5	1.406 (6)	C75—C76	1.397 (6)

N8—C1A—N1	116.1 (4)	C6—C5—C51	118.3 (4)
N8—C1A—C4A	124.9 (4)	C4A—C5—C51	122.7 (4)
N1—C1A—C4A	119.0 (4)	C52—C51—C5	111.0 (4)
C2—N1—C1A	123.3 (4)	N53—C52—C51	178.4 (6)
C2—N1—C11	117.9 (3)	C5—C6—C7	120.5 (4)
C1A—N1—C11	118.8 (3)	N8—C7—C6	121.0 (4)
O21—C2—N1	122.3 (4)	N8—C7—C71	116.3 (4)
O21—C2—N3	120.7 (4)	C6—C7—C71	122.7 (4)
N1—C2—N3	116.9 (4)	C76—C71—C72	118.6 (4)
C4—N3—C2	125.4 (4)	C76—C71—C7	119.9 (4)
C4—N3—C31	117.3 (4)	C72—C71—C7	121.5 (4)
C2—N3—C31	117.2 (4)	C71—C72—C73	120.7 (4)
O41—C4—N3	119.8 (4)	C74—C73—C72	119.6 (4)
O41—C4—C4A	124.8 (4)	C73—C74—C75	120.7 (4)
N3—C4—C4A	115.4 (4)	C73—C74—Br	119.3 (3)
C5—C4A—C1A	116.1 (4)	C75—C74—Br	120.1 (3)
C5—C4A—C4	123.9 (4)	C74—C75—C76	119.3 (4)
C1A—C4A—C4	119.9 (4)	C71—C76—C75	121.0 (4)
C6—C5—C4A	119.1 (4)	C1A—N8—C7	118.3 (3)

N8—C1A—N1—C2	179.0 (4)	C4—C4A—C5—C51	−0.8 (6)
C4A—C1A—N1—C2	−1.0 (6)	C6—C5—C51—C52	−98.7 (5)
N8—C1A—N1—C11	−1.9 (6)	C4A—C5—C51—C52	81.0 (5)
C4A—C1A—N1—C11	178.0 (4)	C4A—C5—C6—C7	−1.4 (6)
C1A—N1—C2—O21	176.7 (4)	C51—C5—C6—C7	178.3 (4)
C11—N1—C2—O21	−2.4 (7)	C5—C6—C7—N8	1.9 (6)
C1A—N1—C2—N3	−0.6 (6)	C5—C6—C7—C71	−178.3 (4)
C11—N1—C2—N3	−179.7 (4)	N8—C7—C71—C76	−0.4 (6)
O21—C2—N3—C4	−176.6 (4)	C6—C7—C71—C76	179.8 (4)
N1—C2—N3—C4	0.7 (6)	N8—C7—C71—C72	−179.0 (4)
O21—C2—N3—C31	7.4 (6)	C6—C7—C71—C72	1.2 (6)
N1—C2—N3—C31	−175.3 (4)	C76—C71—C72—C73	1.0 (7)
C2—N3—C4—O41	−179.7 (4)	C7—C71—C72—C73	179.6 (4)
C31—N3—C4—O41	−3.7 (6)	C71—C72—C73—C74	0.9 (7)
C2—N3—C4—C4A	0.7 (6)	C72—C73—C74—C75	−1.8 (7)
C31—N3—C4—C4A	176.7 (4)	C72—C73—C74—Br	178.1 (3)
N8—C1A—C4A—C5	1.5 (6)	C73—C74—C75—C76	0.8 (7)
N1—C1A—C4A—C5	−178.4 (4)	Br—C74—C75—C76	−179.2 (3)
N8—C1A—C4A—C4	−177.6 (4)	C72—C71—C76—C75	−2.0 (7)
N1—C1A—C4A—C4	2.5 (6)	C7—C71—C76—C75	179.4 (4)
O41—C4—C4A—C5	−0.8 (7)	C74—C75—C76—C71	1.1 (7)
N3—C4—C4A—C5	178.7 (4)	N1—C1A—N8—C7	178.8 (3)
O41—C4—C4A—C1A	178.1 (4)	C4A—C1A—N8—C7	−1.1 (6)
N3—C4—C4A—C1A	−2.3 (6)	C6—C7—N8—C1A	−0.6 (6)
C1A—C4A—C5—C6	−0.2 (6)	C71—C7—N8—C1A	179.5 (3)
C4—C4A—C5—C6	178.8 (4)	C52—N53—H75ⁱ—C75ⁱ	−36
C1A—C4A—C5—C51	−179.8 (4)

Symmetry code: (i) −x+1, −y, −z.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C31—H31B···Brⁱⁱ	0.96	3.07	3.701 (5)	125
C31—H31B···N8ⁱⁱⁱ	0.96	2.81	3.639 (6)	145
C31—H31C···O41^iv	0.96	2.66	3.600 (6)	166
C6—H6···N53^v	0.93	2.76	3.565 (7)	146
C72—H72···N53^v	0.93	2.65	3.476 (7)	148
C73—H73···O21^vi	0.93	2.32	3.223 (6)	165

Symmetry codes: (ii) x+1, y−1, z; (iii) −x+1, −y−1, −z; (iv) −x+2, −y−1, −z; (v) −x+2, −y, −z+1; (vi) x, y+1, z+1.

Experimental details

Crystal data
Chemical formula	C₁₇H₁₃BrN₄O₂
M_r	385.22
Crystal system, space group	Triclinic, P1
Temperature (K)	296
a, b, c (Å)	8.728 (3), 12.087 (4), 8.672 (3)
α, β, γ (°)	108.22 (3), 113.43 (2), 91.24 (3)
V (Å³)	786.1 (5)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	2.63
Crystal size (mm)	0.4 × 0.3 × 0.1

Data collection
Diffractometer	Rigaku AFC-5R diffractometer
Absorption correction	Empirical (using intensity measurements) (TEXSAN; Molecular Structure Corporation/Rigaku Corporation, 1998)
T_min, T_max	0.509, 0.769
No. of measured, independent and observed [I > 2σ(I)] reflections	3619, 3619, 2254
R_int	0.000
(sin θ/λ)_max (Å⁻¹)	0.649

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.043, 0.120, 1.03
No. of reflections	3616
No. of parameters	219
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.48, −0.43

Computer programs: Rigaku/AFC Diffractometer Control Software (Rigaku, 1995), Rigaku/AFC Diffractometer Control Software, TEXSAN (Molecular Structure Corporation/Rigaku Corporation, 1998), SHELXS86 (Sheldrick, 1990), SHELXL93 (Sheldrick, 1993), NRCVAX (Gabe et al.,, 1989), SHELXL93.