5-Chloro-N-[2-(1H-imidazol-4-yl)eth­yl]-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Richter, D.; Kath, J.C.; Rheingold, A.L.; DiPasquale, A.; Yanovsky, A.

doi:10.1107/S1600536809054750

5-Chloro-N-[2-(1H-imidazol-4-yl)ethyl]-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine

D. Richter, J. C. Kath, A. L. Rheingold, A. DiPasquale and A. Yanovsky

The title compound, C₁₂H₁₃ClN₆, was prepared by reaction of 4,5-dichloro-7H-pyrrolo[2,3-d]pyrimidine with 2-(1H-imidazol-4-yl)-N-methylethanamine, and the X-ray study confirmed that chloro-substituent in six-membered ring was replaced in the reaction. The exocyclic N atom environment is approximately coplanar with the pyrrolo[2,3-d]pyrimidine [corresponding dihedral angle is 5.5 (1)°], whereas the mean plane of the N—C—C—C link connecting with the imidazolyl ring is almost exactly orthogonal to the plane of the bicyclic system [dihedral angle = 91.6 (2)°]. The imidazolyl plane itself, however, forms a relatively small dihedral angle of 20.8 (1)° with the pyrrolo[2,3-d]pyrimidine plane. There are two independent N—H

N hydrogen bonds in the structure, which link molecules into layers parallel to ( $\overline{1}$ 03).

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Supporting information

	Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536809054750/dn2525sup1.cif Contains datablocks global, I
	Structure factor file (CIF format) https://doi.org/10.1107/S1600536809054750/dn2525Isup2.hkl Contains datablock I

CCDC reference: 766885

checkCIF report

Key indicators

Single-crystal X-ray study
T = 208 K
Mean (C-C) = 0.003 Å
R factor = 0.043
wR factor = 0.123
Data-to-parameter ratio = 15.4

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT029_ALERT_3_C _diffrn_measured_fraction_theta_full Low .......       0.98
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.600         92
PLAT912_ALERT_4_C Missing # of FCF Reflections Above STh/L=  0.600        163

Alert level G
PLAT128_ALERT_4_G Non-standard setting of Space-group P21/c   ....      P21/n

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   3 ALERT level C = Check and explain
   1 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   2 ALERT type 3 Indicator that the structure quality may be low
   2 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

Comment top

The title compound, C₁₂H₁₃ClN₆, was prepared by reaction of 4,5-dichloro-7H-pyrrolo[2,3-d]pyrimidine with 2-(1H-imidazol-4-yl)-N-methylethanamine, and the present X-ray study confirmed that chloro-substituent in six-membered ring got replaced in this reaction (Fig. 1).

The pyrrolo[2,3-d]pyrimidine system is planar within 0.001 Å, and its least-squares plane, C1/C2/C3/C4/N2/C5/N3/C6/N1 is almost coplanar with the plane C1/N4/C7/C8, the corresponding dihedral angle being equal to 5.5 (1)° (the maximum deviation of the N4 atom from the latter plane being 0.028 (2) Å). The N4—C8—C9—C10 chain linking the bicyclic system with the imidazolyl group may be considered as approximately planar (within 0.130 Å) and its mean plane is orthogonal to the plane of pyrrolopyrimidine [91.6 (2)°]. At the same time the imidazolyl plane forms a relatively small dihedral angle of 20.8 (1)° with the bicyclic system.

The geometric parameters of pyrrolopyrimidin-4-amine system are similar to those observed in related structures (Zabel et al., 1987; Abola & Sundaralingam, 1973), although the title compound provides the first structure with no substitution at the N atom in the pyrrole part. The only other structurally studied compound with disubstituted 4-amino-group (Slauson et al., 2008) shows noticeable non-planarity of the environment of the exocyclic N atom.

There are two independent H-bonds in the structure (Table 1) which link molecules into layers parallel to (-1,0,3) plane (Fig. 2).

Related literature top

For the structures of related compounds with the pyrrolo[2,3-d]pyrimidin-4-amine bicyclic framework, see: Abola & Sundaralingam (1973); Slauson et al. (2008); Zabel et al. (1987).

Experimental top

To a mixture of 4,5-dichloro-7H-pyrrolo[2,3-d]pyrimidine (119 mg, 0.63 mmol) and [2-(1H-imidazol-4-yl)-ethyl]-methylamine (79 mg, 0.63 mmol) dissolved in 2-propanol (1 ml) was added di-isopropyl-ethylamine (0.12 ml, 1.1 eq). The reaction was heated at 80°C for 18 hrs. The solvent was removed and the reaction purified on Si—NH₂ (6% MeOH/EtOAc); product was isolated as colorless solid, 48 mg (27%). 1H NMR (400 MHz, DMSO-d6) δ p.p.m. 2.85 - 2.91 (m, 2 H), 3.22 (s, 3 H), 3.88 (dd, J=8.56, 6.80 Hz, 2 H), 6.78 (s, 1 H), 7.41 (d, J=1.76 Hz, 1 H), 7.52 (d, J=1.01 Hz, 1 H), 8.17 (s, 1 H), 12.05 (s, 1 H).

Computing details top

Data collection: SMART (Bruker, 1997); cell refinement: SAINT (Bruker, 1997); data reduction: SAINT (Bruker, 1997); program(s) used to solve structure: SIR97 (Burla et al., 2005); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-32 (Farrugia, 1997) and PLATON (Spek, 2009); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures top

	Fig. 1. Molecular structure of the title compound, showing 50% probability displacement ellipsoids and atom numbering scheme. H atoms are drawn as circles with arbitrary small radius.
	Fig. 2. Partial packing view of the title compound, viewed down the a axis. Hydrogen bonds are shown as dashed lines. H atoms not involved in hydrogen bondings have been omitted for clarity. [Symmetry code: (i) -x-1/2, y-1/2, -z+1/2]

5-Chloro-N-[2-(1H-imidazol-4-yl)ethyl]-N-methyl- 7H-pyrrolo[2,3-d]pyrimidin-4-amine top

Crystal data top

C₁₂H₁₃ClN₆	F(000) = 576
M_r = 276.73	D_x = 1.476 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 4149 reflections
a = 4.4673 (5) Å	θ = 2.3–27.6°
b = 15.8855 (17) Å	µ = 0.30 mm⁻¹
c = 17.6544 (19) Å	T = 208 K
β = 96.244 (2)°	Rod, colorless
V = 1245.4 (2) Å³	0.16 × 0.08 × 0.08 mm
Z = 4

Data collection top

Bruker SMART CCD area-detector diffractometer	2669 independent reflections
Radiation source: fine-focus sealed tube	2223 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.029
phi and ω scans	θ_max = 27.7°, θ_min = 1.7°
Absorption correction: multi-scan (SADABS; Bruker, 2001)	h = −5→2
T_min = 0.953, T_max = 0.976	k = −20→19
8932 measured reflections	l = −22→22

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) = 0.123	H-atom parameters constrained
S = 1.05	w = 1/[σ²(F_o²) + (0.0625P)² + 0.5128P] where P = (F_o² + 2F_c²)/3
2669 reflections	(Δ/σ)_max = 0.001
173 parameters	Δρ_max = 0.38 e Å⁻³
0 restraints	Δρ_min = −0.55 e Å⁻³

Crystal data top

C₁₂H₁₃ClN₆	V = 1245.4 (2) Å³
M_r = 276.73	Z = 4
Monoclinic, P2₁/n	Mo Kα radiation
a = 4.4673 (5) Å	µ = 0.30 mm⁻¹
b = 15.8855 (17) Å	T = 208 K
c = 17.6544 (19) Å	0.16 × 0.08 × 0.08 mm
β = 96.244 (2)°

Data collection top

Bruker SMART CCD area-detector diffractometer	2669 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2001)	2223 reflections with I > 2σ(I)
T_min = 0.953, T_max = 0.976	R_int = 0.029
8932 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.043	0 restraints
wR(F²) = 0.123	H-atom parameters constrained
S = 1.05	Δρ_max = 0.38 e Å⁻³
2669 reflections	Δρ_min = −0.55 e Å⁻³
173 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 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.

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

	x	y	z	U_iso*/U_eq
C1	−0.0192 (4)	0.58232 (11)	0.29931 (10)	0.0283 (4)
C2	−0.1622 (4)	0.50275 (10)	0.28217 (10)	0.0277 (4)
C3	−0.1729 (4)	0.41555 (11)	0.30729 (11)	0.0328 (4)
C4	−0.3817 (4)	0.37368 (12)	0.25972 (11)	0.0358 (4)
H4	−0.4315	0.3165	0.2638	0.043*
C5	−0.3795 (4)	0.50431 (11)	0.21665 (10)	0.0297 (4)
C6	−0.2998 (4)	0.63935 (11)	0.19349 (11)	0.0351 (4)
H6	−0.3424	0.6876	0.1634	0.042*
C7	0.2759 (5)	0.53923 (14)	0.41905 (14)	0.0525 (6)
H7A	0.0959	0.5146	0.4359	0.079*
H7B	0.3892	0.5680	0.4614	0.079*
H7C	0.3992	0.4952	0.4004	0.079*
C8	0.3331 (4)	0.68204 (12)	0.36897 (11)	0.0346 (4)
H8A	0.3273	0.7100	0.3194	0.042*
H8B	0.5448	0.6750	0.3891	0.042*
C9	0.1773 (4)	0.73809 (12)	0.42332 (11)	0.0339 (4)
H9A	−0.0034	0.7630	0.3957	0.041*
H9B	0.1139	0.7035	0.4647	0.041*
C10	0.3803 (4)	0.80697 (11)	0.45646 (10)	0.0297 (4)
C11	0.5339 (4)	0.81184 (12)	0.52734 (11)	0.0344 (4)
H11	0.5279	0.7730	0.5673	0.041*
C12	0.6424 (4)	0.92068 (12)	0.45984 (11)	0.0354 (4)
H12	0.7291	0.9715	0.4459	0.042*
N1	−0.0952 (3)	0.64914 (9)	0.25352 (9)	0.0331 (3)
N2	−0.5079 (3)	0.42744 (9)	0.20513 (9)	0.0336 (3)
H2	−0.6479	0.4145	0.1688	0.040*
N3	−0.4509 (3)	0.57078 (10)	0.17064 (9)	0.0340 (3)
N4	0.1919 (3)	0.59882 (10)	0.35853 (9)	0.0351 (4)
N5	0.4505 (3)	0.87609 (10)	0.41396 (9)	0.0325 (3)
N6	0.6992 (3)	0.88485 (10)	0.52872 (9)	0.0357 (4)
H6A	0.8182	0.9042	0.5670	0.043*
Cl1	0.02168 (14)	0.36102 (3)	0.38240 (3)	0.0529 (2)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0312 (8)	0.0258 (8)	0.0273 (9)	0.0014 (6)	0.0001 (6)	−0.0027 (7)
C2	0.0335 (8)	0.0243 (8)	0.0244 (9)	0.0013 (6)	−0.0012 (6)	−0.0004 (6)
C3	0.0414 (9)	0.0262 (9)	0.0291 (9)	−0.0002 (7)	−0.0047 (7)	0.0041 (7)
C4	0.0457 (10)	0.0258 (9)	0.0344 (10)	−0.0026 (7)	−0.0026 (7)	0.0009 (7)
C5	0.0339 (8)	0.0264 (9)	0.0277 (9)	0.0022 (7)	−0.0018 (6)	−0.0023 (7)
C6	0.0470 (10)	0.0275 (9)	0.0297 (10)	0.0045 (7)	−0.0016 (7)	0.0042 (7)
C7	0.0680 (13)	0.0322 (11)	0.0498 (14)	0.0004 (10)	−0.0272 (10)	0.0014 (9)
C8	0.0321 (8)	0.0318 (9)	0.0389 (10)	−0.0054 (7)	−0.0013 (7)	−0.0069 (8)
C9	0.0321 (8)	0.0321 (9)	0.0366 (10)	−0.0037 (7)	−0.0003 (7)	−0.0046 (8)
C10	0.0294 (7)	0.0277 (9)	0.0311 (9)	0.0024 (6)	−0.0005 (6)	−0.0029 (7)
C11	0.0395 (9)	0.0298 (9)	0.0323 (10)	0.0011 (7)	−0.0025 (7)	0.0004 (7)
C12	0.0386 (9)	0.0283 (9)	0.0376 (11)	−0.0030 (7)	−0.0036 (7)	−0.0024 (8)
N1	0.0408 (8)	0.0250 (7)	0.0327 (9)	0.0002 (6)	0.0004 (6)	−0.0001 (6)
N2	0.0387 (7)	0.0285 (8)	0.0312 (8)	−0.0022 (6)	−0.0069 (6)	−0.0021 (6)
N3	0.0415 (8)	0.0282 (8)	0.0301 (8)	0.0048 (6)	−0.0060 (6)	0.0008 (6)
N4	0.0407 (8)	0.0257 (8)	0.0359 (9)	−0.0009 (6)	−0.0090 (6)	−0.0031 (6)
N5	0.0349 (7)	0.0303 (8)	0.0305 (8)	−0.0009 (6)	−0.0048 (6)	−0.0002 (6)
N6	0.0390 (8)	0.0320 (8)	0.0331 (9)	−0.0011 (6)	−0.0094 (6)	−0.0062 (7)
Cl1	0.0763 (4)	0.0314 (3)	0.0444 (3)	−0.0069 (2)	−0.0233 (3)	0.0115 (2)

Geometric parameters (Å, º) top

C1—N1	1.355 (2)	C7—H7C	0.9700
C1—N4	1.355 (2)	C8—N4	1.468 (2)
C1—C2	1.434 (2)	C8—C9	1.531 (3)
C2—C5	1.427 (2)	C8—H8A	0.9800
C2—C3	1.457 (2)	C8—H8B	0.9800
C3—C4	1.359 (3)	C9—C10	1.499 (2)
C3—Cl1	1.7360 (18)	C9—H9A	0.9800
C4—N2	1.363 (2)	C9—H9B	0.9800
C4—H4	0.9400	C10—C11	1.362 (2)
C5—N3	1.349 (2)	C10—N5	1.385 (2)
C5—N2	1.355 (2)	C11—N6	1.374 (2)
C6—N3	1.321 (2)	C11—H11	0.9400
C6—N1	1.331 (2)	C12—N5	1.320 (2)
C6—H6	0.9400	C12—N6	1.342 (2)
C7—N4	1.446 (3)	C12—H12	0.9400
C7—H7A	0.9700	N2—H2	0.8700
C7—H7B	0.9700	N6—H6A	0.8700

N1—C1—N4	114.64 (15)	H8A—C8—H8B	107.8
N1—C1—C2	119.20 (15)	C10—C9—C8	111.87 (14)
N4—C1—C2	126.15 (16)	C10—C9—H9A	109.2
C5—C2—C1	113.83 (15)	C8—C9—H9A	109.2
C5—C2—C3	102.77 (14)	C10—C9—H9B	109.2
C1—C2—C3	143.40 (16)	C8—C9—H9B	109.2
C4—C3—C2	108.69 (15)	H9A—C9—H9B	107.9
C4—C3—Cl1	118.73 (14)	C11—C10—N5	109.35 (16)
C2—C3—Cl1	132.58 (14)	C11—C10—C9	128.54 (17)
C3—C4—N2	109.48 (16)	N5—C10—C9	122.03 (16)
C3—C4—H4	125.3	C10—C11—N6	106.29 (16)
N2—C4—H4	125.3	C10—C11—H11	126.9
N3—C5—N2	123.13 (15)	N6—C11—H11	126.9
N3—C5—C2	126.66 (16)	N5—C12—N6	112.00 (17)
N2—C5—C2	110.21 (15)	N5—C12—H12	124.0
N3—C6—N1	128.55 (17)	N6—C12—H12	124.0
N3—C6—H6	115.7	C6—N1—C1	119.29 (15)
N1—C6—H6	115.7	C5—N2—C4	108.84 (15)
N4—C7—H7A	109.5	C5—N2—H2	125.6
N4—C7—H7B	109.5	C4—N2—H2	125.6
H7A—C7—H7B	109.5	C6—N3—C5	112.45 (15)
N4—C7—H7C	109.5	C1—N4—C7	123.13 (16)
H7A—C7—H7C	109.5	C1—N4—C8	121.64 (15)
H7B—C7—H7C	109.5	C7—N4—C8	115.03 (15)
N4—C8—C9	112.60 (15)	C12—N5—C10	105.27 (16)
N4—C8—H8A	109.1	C12—N6—C11	107.09 (15)
C9—C8—H8A	109.1	C12—N6—H6A	126.5
N4—C8—H8B	109.1	C11—N6—H6A	126.5
C9—C8—H8B	109.1

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···N5ⁱ	0.87	1.98	2.845 (2)	175
N6—H6A···N3ⁱⁱ	0.87	2.04	2.892 (2)	167

Symmetry codes: (i) −x−1/2, y−1/2, −z+1/2; (ii) x+3/2, −y+3/2, z+1/2.

Experimental details

Crystal data
Chemical formula	C₁₂H₁₃ClN₆
M_r	276.73
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	208
a, b, c (Å)	4.4673 (5), 15.8855 (17), 17.6544 (19)
β (°)	96.244 (2)
V (Å³)	1245.4 (2)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.30
Crystal size (mm)	0.16 × 0.08 × 0.08

Data collection
Diffractometer	Bruker SMART CCD area-detector diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2001)
T_min, T_max	0.953, 0.976
No. of measured, independent and observed [I > 2σ(I)] reflections	8932, 2669, 2223
R_int	0.029
(sin θ/λ)_max (Å⁻¹)	0.654

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.043, 0.123, 1.05
No. of reflections	2669
No. of parameters	173
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.38, −0.55

Computer programs: SMART (Bruker, 1997), SAINT (Bruker, 1997), SIR97 (Burla et al., 2005), SHELXL97 (Sheldrick, 2008), ORTEP-32 (Farrugia, 1997) and PLATON (Spek, 2009), WinGX (Farrugia, 1999).