5-(4-Chloro­phen­yl)-7-(4-methyl­phen­yl)-4-(pyrrolidin-1-yl)-7H-pyrrolo­[2,3-d]pyrimidine

Urmila H Patel; Rajesh D Modh; Dhaval A Shah

doi:10.1107/S1600536813019168

. 2013 Jul 20;69(Pt 8):o1286–o1287. doi: 10.1107/S1600536813019168

5-(4-Chlorophenyl)-7-(4-methylphenyl)-4-(pyrrolidin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine

Urmila H Patel ^a,^*, Rajesh D Modh ^a, Dhaval A Shah ^b

PMCID: PMC3793780 PMID: 24109367

Abstract

The title compound, C₂₃H₂₁ClN₄, contains two molecules (A and B) in the asymmetric unit, which are related to one another by a pseudo-inversion center. The non-aromatic pyrrolidine ring in each independent molecule adopts a half-chair conformation; the ring puckering parameters are θ = 0.407 (3) Å and ϕ = 270.5 (4)°, and the pseudo-rotation parameters are ρ = 72.5 (3)° and τ = 42.2 (2)° for an N—C bond of molecule A, and the corresponding values are 0.415 (3) Å, 271.6 (4)°, 73.6 (3)° and 42.6 (2)° for molecule B. The dihedral angles between the central fused-ring system and the substituted chlorophenyl and methylphenyl rings are 66.35 and 45.59°, respectively, for molecule A, and 64.51 and 41.89° for molecule B. The geometry of all four intramolecular C—H⋯π interactions are of type III. π–π interactions involving the centroids of symmetry-related pyrrole rings of molecule B are 4.390 Å, contributing further to the stability of the molecule.

Related literature

For background to and the biological activity of pyrrolo[2,3-d]pyrimidines, see: Chadwick (1990 ▶); Hulzenlaub et al. (1972 ▶); Ohgi et al. (1979 ▶); Smith et al. (1972 ▶). For our crystallographic investigations of heterocyclic compounds, see: Patel et al. (2007 ▶, 2012 ▶). For C—H⋯π interactions, see: Malone et al. (1997 ▶). For puckering parameters, see: Cremer & Pople (1975 ▶). graphic file with name e-69-o1286-scheme1.jpg

Experimental

Crystal data

C₂₃H₂₁ClN₄
M _r = 388.72
Triclinic,
a = 8.967 (3) Å
b = 15.367 (5) Å
c = 15.960 (2) Å
α = 69.210 (17)°
β = 75.653 (16)°
γ = 76.52 (3)°
V = 1966.2 (10) Å³
Z = 4
Mo Kα radiation
μ = 0.21 mm⁻¹
T = 293 K
0.3 × 0.2 × 0.2 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
Absorption correction: ψ scan (North et al., 1968 ▶) T _min = 0.951, T _max = 0.959
7458 measured reflections
6864 independent reflections
3569 reflections with I > 2σ(I)
R _int = 0.027
2 standard reflections every 1 min intensity decay: none

Refinement

R[F ² > 2σ(F ²)] = 0.042
wR(F ²) = 0.125
S = 1.01
6864 reflections
507 parameters
H-atom parameters constrained
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.25 e Å⁻³

Data collection: CAD-4 Software (Enraf–Nonius, 1989 ▶); cell refinement: CAD-4 Software; data reduction: CAD-4 Software; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2009 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536813019168/gg2114sup1.cif

e-69-o1286-sup1.cif^{(33.4KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813019168/gg2114Isup2.hkl

e-69-o1286-Isup2.hkl^{(329.1KB, hkl)}

Click here for additional data file.^{(7.6KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813019168/gg2114Isup3.cml

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

Table 1. Hydrogen-bond geometry (Å, °).

Cg1, Cg2, Cg3 and Cg4 are the centroids of the N6/C5/C4/C9/N8/C7, N34/C33/C32/C37/N36/C35, C17–C22 and C45–C50 rings, respectively.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C18—H18⋯Cg1ⁱ	0.93	2.68	3.483 (3)	144
C46—H46⋯Cg2ⁱⁱ	0.93	2.73	3.549 (3)	147
C25—H251⋯Cg3	0.97	2.79	3.462 (3)	127
C53—H531⋯Cg4	0.97	2.84	3.506 (3)	127

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

The authors are thankful to Department of Physics, SPU, for providing the financial support to carry out this work and to Dr Babu Varghese of RSIC, IIT Madras, for helping us with the data collection. RDM is thankful to the UGC, New Delhi, for the UGC teacher fellowship under the FIP scheme and to Gujarat Arts and Science College, Ahmedabad, for allowing the research work to be carried out under the FIP scheme.

supplementary crystallographic information

Comment

Pyrrolo[2,3-d]pyrimidine belongs to an important class of biologically active heterocyclic compounds, structurally closely related to nucleosides and some antibiotics (Chadwick, 1990; Ohgi et al., 1979). These group of compounds are very well recognized for their biological activities such as anti-tumor, anti-allergic, anti-viral and anti-inflammatory (Hulzenlaub et al., 1972; Smith et al., 1972). As a part of a continuation of our crystallographic investigations of heterocyclic compounds (Patel et al., 2007; Patel et al., 2012), we now report herein the supra-molecular structure of a fused pyrrolo[2,3-d]pyrimidine derivative.

Two independent molecules A and B of the asymmetric unit [Fig.1] have similar conformations. The fused pyrrolo pyrimidine rings of A and B in the title compound are practically planar with a dihedral angle of 4.11 (16)° in A and 3.00 (17)° in B. The observed bond lengths and bond angles indicate a significant amount of strain arising due to fusion. A close observation of the molecular geometry: bond lengths, bond angles including torsional angles of both molecules A and B reveals that two independent molecules of the asymmetric unit are related to each other by a pseudoinversion center. The aromatic pyrrolodine ring of both molecules is puckered to adopt half chair conformation. The ring puckering parameters for mol A corresponding to the atom sequence N24—C25—C26—C27—C28 (Cremer et al., 1975) are Theta = 0.407 (3)° and Phi = 270.5 (4)° and pseudo rotation parameters are Rho = 72.5 (3)° and t = 42.2 (2)° for N24—C25 bond and those of molecule B are Theta = 0.415 (3)° and Phi = 271.6 (4)° for the atom sequence N52—C53—C54—C55—C56 and the pseudo rotation parameters Rho = 73.6 (3)° and t = 42.6 (2)° for N52—C53 bond confirming a half chair conformation. The conformation of the substituents chlorophenyl, methylphenyl and pyrrolodine of both molecules are very similar. Torsional angles C4—C5—N24—C28 (177.9 (3)°) and C32—C33—N52—C53 (177.9 (3)°) confirm an extended conformation of the pyrrolodine ring with respect to fused ring system where as chlorophenyl ring of both molecules indicates a maximum turn, with dihedral angle of 66.35° (A)and 64.51°(B) between the said ring and fused system. The tolyl ring of both molecules are twisted by 44.59° and 41.89° for A and B, respectively.

In the absence of potential donor-acceptor groups in these heterocyclic compounds, the stability of supra-molecular structure is mainly due to relatively weak but significant C—H···π, π–π interactions. Molecule A and its centro-symmetry related pair gets superimposed centering at 0,0,1. The molecular aggregate so formed are held together by two pairs of C—H···π hydrogen bonds [Fig.2], one intra involving C25—H251 with Cg(3) (the centroid of the ring C17—C18—C19—C20—C21—C22) and the other intermolecular involving C18—H18 with Cg(1) (the centroid of the ring N6—C5—C4—C9—N8—C7) at 1-x, -y, 1-z. The C—H···π interactions involving molecule B and its symmetry related partner is very similar to that of molecule A but this time centered at 0,1,0. The intramolecular hydrogen bond involves C53—H531 to Cg(4) (the centroid of the ring C45—C46—C47—C48—C49—C50) and the intermolecular hydrogen bond is between C46—H46 with Cg(2) (the centroid of the ring N34—C33—C32—C37—N36—C35) at -x, 1 - y, 2 - z. The details of the geometry of these interation is in Table 1. The striking feature of the C—H···π hydrogen bond is that these interactions do not interlink molecules A and B, but it involves only individual molecules. The interactions involve the same group of moieties of the two molecules and is of same length. All of the four C—H···π interactions are of type-III as described by Malone et al., 1997, indicating an exact similarities in the C—H···π interactions. In addition, direction specific π–π interaction involving symmetry related pyrrole ring of molecule B at -1-x, 1-y, 2-z contribute further to the stability of molecular packing along the [100] direction; their centroids are seperated by 4.390 Å [Fig.3]. However,this interaction is absent in molecule A. In the molecule, the closest approach distance between two symmetry (x - 1,-y + 1, Z+1) related chlorines is 3.883 (2) Å.

Experimental

A uniform mixture of 4-chloro-5-(4-Chlorophenyl)-7-(4-methylphenyl)-7H- pyrrolo[2,3-d]pyrimidine and pyrrolodine was heated in an oil bath at 80–90° C with stirring. The heating was continued till the starting compound was consumed. The pH of reaction mixture was maintained and the final product was separated from a mixture of ethanol and N,N-dimethylformamide.