7-Cyclo­pentyl-5-(4-phenoxy­phenyl)-7H-pyrrolo­[2,3-d]­pyrimidine-4-yl­amine, an lck tyrosine kinase inhibitor

The molecular and crystal structures of the potent and selective lck tyrosine kinase inhibitor, C₂₃H₂₂N₄O, have been determined by single-crystal X-ray diffraction. The pyrrolo­pyrimidine and phenyl rings are planar while the cyclo­pentyl ring adopts a conformation between envelope and half-chair. The overall conformation is defined by the spatial arrangement of the ring moieties.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.009 Å
• R factor = 0.061
• wR factor = 0.136
• Data-to-parameter ratio = 15.5

checkCIF results

No syntax errors found



ADDSYM reports no extra symmetry


 Alert Level C:



PLAT_420  Alert C D-H Without Acceptor       N(41)  -   H(41B)            ?


 0 Alert Level A = Potentially serious problem

 0 Alert Level B = Potential problem

 1 Alert Level C = Please check

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Computing details

Data collection: EXPRESS in CAD-4 Software (Enraf-Nonius, 1989); cell refinement: SET4 and CELDIM in CAD-4 Software; data reduction: HELENA (Spek, 1997); program(s) used to solve structure: SIR97 (Altomare et al., 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 1998); software used to prepare material for publication: PLATON.

7-Cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidine-4-ylamine

Crystal data

C23H22N4O	F(000) = 1568
Mr = 370.45	Dx = 1.275 Mg m^−3
Orthorhombic, Pbca	Mo Kα radiation, λ = 0.71069 Å
Hall symbol: -P 2ac 2ab	Cell parameters from 25 reflections
a = 11.914 (2) Å	θ = 3.1–10.6°
b = 12.399 (5) Å	µ = 0.08 mm^−1
c = 26.133 (5) Å	T = 293 K
V = 3860.4 (18) Å^3	Prism, colourless
Z = 8	0.20 × 0.16 × 0.15 mm

Data collection

Enraf-Nonius CAD-4 diffractometer	Rint = 0.000
Radiation source: X-ray tube	θmax = 26.3°, θmin = 2.3°
Graphite monochromator	h = 0→14
ω/2θ scans	k = −15→0
3910 measured reflections	l = 0→32
3910 independent reflections	3 standard reflections every 120 min
819 reflections with I > 2σ(I)	intensity decay: none

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.061	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.136	See text
S = 0.84	w = 1/[σ^2(Fo^2) + (0.0182P)^2] where P = (Fo^2 + 2Fc^2)/3
3910 reflections	(Δ/σ)max = 0.001
253 parameters	Δρmax = 0.20 e Å^−3
0 restraints	Δρmin = −0.23 e Å^−3
0 constraints

Special details

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All e.s.d.'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 on F^{2 for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F}2, conventional R-factors R are based on F, with F set to zero for negative F^{2. The observed criterion of F}2 > σ(F^{2) is used only for calculating -R-factor-obs etc. and is not relevant to the choice of reflections for refinement. R-factors based on F}2 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 (Ų)

	x	y	z	Uiso*/Ueq
O16	0.2541 (4)	−0.1436 (4)	0.68577 (16)	0.0727 (19)
N1	−0.2088 (4)	0.3298 (3)	0.52631 (17)	0.0390 (17)
N3	−0.2389 (4)	0.1407 (4)	0.51220 (18)	0.0440 (17)
N7	−0.0508 (4)	0.3681 (4)	0.58142 (18)	0.0433 (19)
N41	−0.1340 (4)	0.0086 (3)	0.54859 (15)	0.051 (2)
C2	−0.2611 (4)	0.2454 (5)	0.5062 (2)	0.049 (2)
C4	−0.1503 (5)	0.1147 (5)	0.5410 (2)	0.035 (2)
C5	0.0086 (5)	0.2000 (5)	0.5984 (2)	0.038 (3)
C6	0.0265 (4)	0.3071 (5)	0.6072 (2)	0.043 (3)
C8	−0.1191 (5)	0.2997 (5)	0.5546 (2)	0.037 (2)
C9	−0.0834 (5)	0.1944 (5)	0.5634 (2)	0.033 (2)
C10	0.0740 (5)	0.1104 (5)	0.6210 (2)	0.035 (2)
C11	0.1189 (4)	0.0271 (4)	0.5922 (2)	0.041 (2)
C12	0.1759 (4)	−0.0555 (5)	0.6151 (2)	0.042 (2)
C13	0.1929 (5)	−0.0577 (5)	0.6675 (3)	0.047 (3)
C14	0.1537 (5)	0.0264 (5)	0.6967 (2)	0.053 (3)
C15	0.0930 (5)	0.1086 (4)	0.6737 (2)	0.047 (3)
C17	0.2673 (6)	−0.1556 (5)	0.7384 (3)	0.048 (3)
C18	0.2003 (6)	−0.2244 (6)	0.7635 (3)	0.063 (3)
C19	0.2193 (6)	−0.2440 (6)	0.8148 (3)	0.073 (3)
C20	0.3041 (7)	−0.1921 (6)	0.8393 (3)	0.071 (3)
C21	0.3716 (6)	−0.1223 (6)	0.8139 (3)	0.083 (4)
C22	0.3536 (7)	−0.1054 (6)	0.7630 (3)	0.077 (4)
C71	−0.0632 (5)	0.4861 (4)	0.5846 (2)	0.051 (3)
C72	−0.0838 (6)	0.5261 (5)	0.6392 (2)	0.078 (3)
C73	0.0152 (7)	0.5947 (6)	0.6527 (3)	0.093 (4)
C74	0.0557 (6)	0.6381 (6)	0.6025 (3)	0.095 (4)
C75	0.0411 (5)	0.5452 (5)	0.5660 (2)	0.063 (3)
H2	−0.32160	0.26140	0.48500	0.0580*
H6	0.08320	0.33470	0.62790	0.0520*
H11	0.11000	0.02730	0.55690	0.0490*
H12	0.20390	−0.11140	0.59500	0.0510*
H14	0.16790	0.02830	0.73170	0.0640*
H15	0.06410	0.16380	0.69390	0.0570*
H18	0.14160	−0.25860	0.74660	0.0750*
H19	0.17430	−0.29260	0.83250	0.0870*
H20	0.31600	−0.20450	0.87390	0.0860*
H21	0.42910	−0.08650	0.83090	0.1000*
H22	0.40070	−0.05930	0.74490	0.0930*
H41A	−0.17920	−0.03740	0.53520	0.0600*
H41B	−0.07830	−0.01310	0.56680	0.0600*
H71	−0.12690	0.50780	0.56320	0.0600*
H72A	−0.15250	0.56790	0.64090	0.0940*
H72B	−0.08990	0.46570	0.66260	0.0940*
H73A	0.07310	0.55210	0.66910	0.1110*
H73B	−0.00670	0.65280	0.67540	0.1110*
H74A	0.13380	0.65970	0.60460	0.1140*
H74B	0.01120	0.69970	0.59180	0.1140*
H75A	0.10610	0.49810	0.56690	0.0750*
H75B	0.03080	0.57110	0.53130	0.0750*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O16	0.093 (4)	0.080 (3)	0.045 (3)	0.044 (3)	−0.003 (3)	0.006 (3)
N1	0.036 (3)	0.039 (3)	0.042 (3)	0.003 (3)	−0.002 (3)	−0.006 (3)
N3	0.043 (3)	0.032 (3)	0.057 (3)	0.000 (3)	−0.017 (3)	0.000 (3)
N7	0.043 (3)	0.027 (3)	0.060 (4)	0.003 (3)	−0.011 (3)	−0.004 (3)
N41	0.054 (4)	0.029 (3)	0.069 (4)	−0.007 (3)	−0.016 (3)	−0.003 (3)
C2	0.042 (4)	0.051 (4)	0.053 (4)	0.006 (4)	−0.008 (4)	0.001 (4)
C4	0.045 (4)	0.028 (4)	0.033 (4)	−0.005 (4)	0.011 (3)	0.002 (3)
C5	0.047 (5)	0.033 (4)	0.034 (4)	0.003 (4)	0.002 (3)	0.003 (4)
C6	0.031 (4)	0.052 (5)	0.046 (4)	−0.007 (4)	−0.006 (3)	−0.009 (4)
C8	0.039 (4)	0.033 (4)	0.038 (4)	−0.011 (4)	0.001 (4)	0.000 (4)
C9	0.038 (4)	0.029 (4)	0.031 (4)	−0.004 (4)	0.002 (3)	−0.004 (3)
C10	0.033 (4)	0.040 (4)	0.033 (4)	−0.005 (4)	0.001 (3)	0.001 (4)
C11	0.031 (4)	0.048 (4)	0.044 (4)	0.005 (3)	−0.007 (3)	0.007 (4)
C12	0.046 (4)	0.050 (4)	0.031 (4)	0.003 (4)	0.005 (4)	−0.008 (4)
C13	0.044 (5)	0.051 (5)	0.046 (5)	0.007 (4)	0.001 (4)	0.000 (4)
C14	0.058 (5)	0.063 (5)	0.038 (4)	0.014 (4)	−0.001 (4)	−0.009 (4)
C15	0.044 (5)	0.044 (4)	0.054 (5)	0.016 (4)	0.004 (4)	−0.008 (4)
C17	0.060 (6)	0.042 (4)	0.042 (5)	0.025 (4)	0.005 (5)	0.010 (4)
C18	0.058 (5)	0.077 (6)	0.053 (5)	0.001 (5)	0.000 (4)	0.004 (5)
C19	0.063 (6)	0.084 (6)	0.072 (6)	0.000 (5)	0.023 (5)	0.027 (5)
C20	0.063 (6)	0.095 (6)	0.055 (5)	0.037 (5)	−0.007 (5)	0.015 (5)
C21	0.077 (7)	0.106 (7)	0.066 (6)	−0.013 (5)	−0.005 (5)	0.002 (6)
C22	0.086 (7)	0.084 (6)	0.062 (6)	−0.024 (5)	0.010 (5)	0.013 (5)
C71	0.053 (5)	0.031 (4)	0.068 (5)	−0.001 (4)	−0.012 (4)	−0.003 (4)
C72	0.113 (7)	0.046 (5)	0.076 (6)	−0.008 (5)	0.033 (6)	−0.020 (4)
C73	0.099 (7)	0.079 (6)	0.100 (7)	0.020 (5)	−0.038 (6)	−0.030 (6)
C74	0.091 (6)	0.065 (6)	0.129 (8)	−0.027 (5)	0.006 (6)	−0.033 (6)
C75	0.071 (5)	0.047 (4)	0.070 (5)	−0.016 (4)	0.009 (5)	−0.001 (4)

Geometric parameters (Å, º)

O16—C13	1.376 (8)	C20—C21	1.355 (11)
O16—C17	1.392 (9)	C21—C22	1.364 (11)
N1—C2	1.326 (7)	C71—C75	1.522 (8)
N1—C8	1.352 (7)	C71—C72	1.530 (8)
N3—C2	1.334 (8)	C72—C73	1.496 (11)
N3—C4	1.336 (7)	C73—C74	1.498 (11)
N7—C6	1.369 (7)	C74—C75	1.506 (10)
N7—C8	1.368 (8)	C2—H2	0.9305
N7—C71	1.473 (7)	C6—H6	0.9306
N41—C4	1.345 (7)	C11—H11	0.9286
N41—H41A	0.8589	C12—H12	0.9314
N41—H41B	0.8598	C14—H14	0.9305
C4—C9	1.398 (8)	C15—H15	0.9304
C5—C9	1.429 (8)	C18—H18	0.9295
C5—C10	1.480 (8)	C19—H19	0.9298
C5—C6	1.364 (9)	C20—H20	0.9281
C8—C9	1.392 (9)	C21—H21	0.9294
C10—C15	1.396 (7)	C22—H22	0.9302
C10—C11	1.385 (8)	C71—H71	0.9804
C11—C12	1.367 (8)	C72—H72A	0.9698
C12—C13	1.385 (9)	C72—H72B	0.9696
C13—C14	1.374 (9)	C73—H73A	0.9688
C14—C15	1.387 (8)	C73—H73B	0.9690
C17—C18	1.340 (10)	C74—H74A	0.9698
C17—C22	1.363 (11)	C74—H74B	0.9709
C18—C19	1.381 (11)	C75—H75A	0.9702
C19—C20	1.358 (11)	C75—H75B	0.9698
O16···C6^i	3.380 (7)	H2···C5^xi	3.0119
O16···H6^i	2.4732	H6···C15	3.0505
N1···N41^ii	2.960 (6)	H6···H75A	2.5924
N41···C11	3.230 (7)	H6···O16^vii	2.4732
N41···C10	3.364 (7)	H11···N41	2.9243
N41···N1^iii	2.960 (6)	H11···H41B	2.3132
N1···H75B^iv	2.8764	H11···N41^vi	2.8071
N1···H20^v	2.9347	H11···H41A^vi	2.5472
N1···H71	2.5985	H12···N3^vi	2.8555
N1···H41A^ii	2.1321	H14···C17	2.5753
N3···H71^iii	2.6548	H14···C22	2.8831
N3···H12^vi	2.8555	H15···C6	2.9140
N41···H11	2.9243	H19···C5^viii	2.8315
N41···H11^vi	2.8071	H19···C9^viii	2.9325
N41···H71^iii	2.8741	H20···N1^viii	2.9347
C6···O16^vii	3.380 (7)	H20···C8^viii	2.9995
C8···C20^v	3.543 (10)	H22···H73A^i	2.4350
C10···N41	3.364 (7)	H41A···H11^vi	2.5472
C11···N41	3.230 (7)	H41A···N1^iii	2.1321
C14···C22	3.368 (10)	H41A···C2^iii	2.8867
C20···C8^viii	3.543 (10)	H41A···H71^iii	2.4872
C22···C14	3.368 (10)	H41B···C5	2.9555
C2···H41A^ii	2.8867	H41B···C10	2.7647
C4···H71^iii	3.0232	H41B···C11	2.4918
C5···H41B	2.9555	H41B···H11	2.3132
C5···H19^v	2.8315	H71···N1	2.5985
C5···H2^ix	3.0119	H71···N3^ii	2.6548
C6···H75A	2.7599	H71···N41^ii	2.8741
C6···H15	2.9140	H71···C4^ii	3.0232
C6···H72B	2.8082	H71···H41A^ii	2.4872
C8···H20^v	2.9995	H72A···C19^xii	3.0187
C8···H75B^iv	2.9516	H72A···C20^xii	3.0644
C9···H19^v	2.9325	H72B···C6	2.8082
C10···H41B	2.7647	H72B···C19^v	3.0799
C11···H41B	2.4918	H73A···H22^vii	2.4350
C12···H75A^i	2.9621	H73B···C20^xii	2.9878
C15···H6	3.0505	H75A···C6	2.7599
C17···H14	2.5753	H75A···H6	2.5924
C19···H72B^viii	3.0799	H75A···C12^vii	2.9621
C19···H72A^x	3.0187	H75B···N1^iv	2.8764
C20···H72A^x	3.0644	H75B···C8^iv	2.9516
C20···H73B^x	2.9878	H75B···C75^iv	3.0461
C22···H14	2.8831	H75B···H75B^iv	2.5147
C75···H75B^iv	3.0461
C13—O16—C17	119.0 (5)	C71—C75—C74	105.1 (5)
C2—N1—C8	111.7 (4)	N1—C2—H2	115.57
C2—N3—C4	117.2 (5)	N3—C2—H2	115.53
C6—N7—C8	108.0 (5)	N7—C6—H6	124.84
C6—N7—C71	126.1 (5)	C5—C6—H6	124.70
C8—N7—C71	125.8 (5)	C10—C11—H11	119.58
H41A—N41—H41B	120.11	C12—C11—H11	119.58
C4—N41—H41A	119.94	C11—C12—H12	119.25
C4—N41—H41B	119.96	C13—C12—H12	119.39
N1—C2—N3	128.9 (5)	C13—C14—H14	120.22
N41—C4—C9	123.2 (5)	C15—C14—H14	120.15
N3—C4—N41	115.7 (5)	C10—C15—H15	119.21
N3—C4—C9	121.1 (6)	C14—C15—H15	119.19
C6—C5—C9	106.0 (5)	C17—C18—H18	120.40
C6—C5—C10	125.5 (5)	C19—C18—H18	120.28
C9—C5—C10	128.5 (5)	C18—C19—H19	120.16
N7—C6—C5	110.5 (5)	C20—C19—H19	120.10
N7—C8—C9	108.4 (5)	C19—C20—H20	119.63
N1—C8—C9	126.2 (5)	C21—C20—H20	119.50
N1—C8—N7	125.4 (5)	C20—C21—H21	120.55
C5—C9—C8	107.1 (5)	C22—C21—H21	120.59
C4—C9—C8	114.8 (5)	C17—C22—H22	119.72
C4—C9—C5	137.7 (6)	C21—C22—H22	119.71
C5—C10—C11	123.1 (5)	N7—C71—H71	108.55
C5—C10—C15	119.4 (5)	C72—C71—H71	108.59
C11—C10—C15	117.5 (5)	C75—C71—H71	108.52
C10—C11—C12	120.8 (5)	C71—C72—H72A	110.56
C11—C12—C13	121.4 (5)	C71—C72—H72B	110.47
O16—C13—C14	125.1 (6)	C73—C72—H72A	110.53
O16—C13—C12	115.8 (6)	C73—C72—H72B	110.45
C12—C13—C14	119.0 (6)	H72A—C72—H72B	108.70
C13—C14—C15	119.6 (5)	C72—C73—H73A	110.83
C10—C15—C14	121.6 (5)	C72—C73—H73B	110.77
C18—C17—C22	120.6 (7)	C74—C73—H73A	110.73
O16—C17—C18	119.0 (6)	C74—C73—H73B	110.85
O16—C17—C22	120.2 (6)	H73A—C73—H73B	109.04
C17—C18—C19	119.3 (7)	C73—C74—H74A	111.02
C18—C19—C20	119.7 (7)	C73—C74—H74B	111.04
C19—C20—C21	120.9 (7)	C75—C74—H74A	110.98
C20—C21—C22	118.9 (7)	C75—C74—H74B	110.87
C17—C22—C21	120.6 (7)	H74A—C74—H74B	108.84
C72—C71—C75	105.8 (5)	C71—C75—H75A	110.74
N7—C71—C72	113.0 (4)	C71—C75—H75B	110.77
N7—C71—C75	112.2 (5)	C74—C75—H75A	110.67
C71—C72—C73	106.1 (5)	C74—C75—H75B	110.71
C72—C73—C74	104.6 (6)	H75A—C75—H75B	108.84
C73—C74—C75	104.1 (6)
N1—C8—C9—C5	−175.5 (5)	C6—C5—C9—C8	−2.4 (6)
N7—C8—C9—C4	176.0 (5)	C10—C5—C9—C4	6.0 (11)
C6—C5—C10—C11	−130.1 (6)	C9—C5—C6—N7	2.1 (6)
C6—C5—C10—C15	49.4 (8)	C10—C5—C9—C8	178.1 (5)
C9—C5—C10—C11	49.3 (9)	N1—C8—C9—C4	−1.3 (8)
C9—C5—C10—C15	−131.2 (6)	N7—C8—C9—C5	1.8 (6)
C12—C13—O16—C17	−175.2 (5)	C15—C10—C11—C12	2.4 (8)
C14—C13—O16—C17	8.3 (9)	C5—C10—C15—C14	180.0 (9)
C13—O16—C17—C18	98.4 (7)	C5—C10—C11—C12	−178.1 (5)
C13—O16—C17—C22	−87.4 (8)	C11—C10—C15—C14	−0.5 (9)
C6—N7—C71—C72	−57.3 (7)	C10—C11—C12—C13	−1.4 (8)
C6—N7—C71—C75	62.2 (7)	C11—C12—C13—O16	−178.3 (5)
C8—N7—C71—C72	118.3 (6)	C11—C12—C13—C14	−1.5 (9)
C8—N7—C71—C75	−122.1 (6)	C12—C13—C14—C15	3.4 (9)
C2—N1—C8—C9	−0.9 (8)	O16—C13—C14—C15	179.9 (7)
C8—N1—C2—N3	2.9 (8)	C13—C14—C15—C10	−2.4 (9)
C2—N1—C8—N7	−177.8 (5)	O16—C17—C22—C21	−175.7 (7)
C4—N3—C2—N1	−2.2 (8)	C18—C17—C22—C21	−1.6 (11)
C2—N3—C4—C9	−0.6 (8)	O16—C17—C18—C19	174.3 (6)
C2—N3—C4—N41	176.4 (5)	C22—C17—C18—C19	0.1 (12)
C8—N7—C6—C5	−1.1 (6)	C17—C18—C19—C20	1.1 (11)
C71—N7—C6—C5	175.2 (5)	C18—C19—C20—C21	−1.0 (12)
C6—N7—C8—N1	176.8 (5)	C19—C20—C21—C22	−0.5 (12)
C6—N7—C8—C9	−0.5 (6)	C20—C21—C22—C17	1.8 (11)
C71—N7—C8—N1	0.5 (9)	N7—C71—C75—C74	−140.1 (5)
C71—N7—C8—C9	−176.8 (5)	C72—C71—C75—C74	−16.4 (6)
N3—C4—C9—C8	2.1 (8)	N7—C71—C72—C73	116.2 (6)
N41—C4—C9—C5	−3.0 (11)	C75—C71—C72—C73	−7.0 (6)
N41—C4—C9—C8	−174.7 (5)	C71—C72—C73—C74	27.9 (7)
N3—C4—C9—C5	173.8 (6)	C72—C73—C74—C75	−38.3 (7)
C6—C5—C9—C4	−174.5 (7)	C73—C74—C75—C71	33.8 (7)
C10—C5—C6—N7	−178.4 (5)

Symmetry codes: (i) −x+1/2, y−1/2, z; (ii) −x−1/2, y+1/2, z; (iii) −x−1/2, y−1/2, z; (iv) −x, −y+1, −z+1; (v) −x, y+1/2, −z+3/2; (vi) −x, −y, −z+1; (vii) −x+1/2, y+1/2, z; (viii) −x, y−1/2, −z+3/2; (ix) x+1/2, −y+1/2, −z+1; (x) x+1/2, y−1, −z+3/2; (xi) x−1/2, −y+1/2, −z+1; (xii) x−1/2, y+1, −z+3/2.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N41—H41A···N1^iii	0.86	2.13	2.960 (6)	162
C6—H6···O16^vii	0.93	2.47	3.380 (7)	165
C71—H71···N1	0.98	2.60	3.014 (7)	106

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