5-Butyl­amino-6-(4-fluoro­phen­yl)-7-oxo-1-p-tolyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidine-3-carbonitrile

Ji-Huan Hu; Ming-Hu Wu

doi:10.1107/S1600536808009744

. 2008 Apr 16;64(Pt 5):o845. doi: 10.1107/S1600536808009744

5-Butylamino-6-(4-fluorophenyl)-7-oxo-1-p-tolyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidine-3-carbonitrile

Ji-Huan Hu ^a, Ming-Hu Wu ^b,^*

PMCID: PMC2961236 PMID: 21202333

Abstract

In the title compound, C₂₃H₂₁FN₆O, the dihedral angle between the fluorophenyl and pyrimidinone rings is 75.9 (1)°, and the dihedral angle between the methylphenyl and pyrazole rings is 40.3 (1)°. In the crystal structure, weak C—H⋯π(arene) and C—N⋯π(arene) interactions and intermolecular C—H⋯N and N—H⋯O hydrogen-bonding interactions are present.

Related literature

For background information, see: Bell et al. (1991 ▶); Zhao et al. (2006 ▶); Allerton et al. (2006 ▶).

Experimental

Crystal data

C₂₃H₂₁FN₆O
M _r = 416.46
Monoclinic,
a = 11.8800 (5) Å
b = 9.36020 (4) Å
c = 19.0053 (8) Å
β = 91.178 (1)°
V = 2112.93 (13) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 295 (2) K
0.30 × 0.20 × 0.20 mm

Data collection

Bruker SMART APEX CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2001 ▶) T _min = 0.973, T _max = 0.982
12013 measured reflections
3704 independent reflections
3085 reflections with I > 2σ(I)
R _int = 0.031

Refinement

R[F ² > 2σ(F ²)] = 0.055
wR(F ²) = 0.154
S = 1.11
3704 reflections
285 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.26 e Å⁻³

Data collection: SMART (Bruker, 2001 ▶); cell refinement: SAINT (Bruker, 2001 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2003 ▶); software used to prepare material for publication: PLATON.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808009744/er2051sup1.cif

e-64-0o845-sup1.cif^{(22.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808009744/er2051Isup2.hkl

e-64-0o845-Isup2.hkl^{(181.6KB, hkl)}

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

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

Cg1 is the centroid of the C14–C19 ring and Cg2 is the centroid of the N4/C9/C10/C13/N5/C12 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N6—H6A⋯O1ⁱ	0.861 (10)	2.32 (2)	2.904 (2)	125 (2)
C15—H15⋯N3ⁱⁱ	0.93	2.58	3.449 (3)	155
C19—H19⋯N3ⁱⁱⁱ	0.93	2.50	3.219 (3)	134
C6—H6⋯Cg1^iv	0.93	2.82	3.671 (2)	152
C11—N3⋯Cg2^v	1.141 (3)	3.621 (3)	3.710 (3)	85.4 (2)

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) ; (v) .

Acknowledgments

The authors gratefully acknowledge financial support of this work as a project of the Natural Science Foundation of Hubei Province under grant No. 2006ABA334.

supplementary crystallographic information

Comment

Pyrazolo[4,3-d]pyrimidin-7-ones have been reported as potent and selective inhibitors of PDE5 (Bell et al., 1991; Zhao et al., 2006). Sildenafil citrate, a pyrazolo[4,3-d]pyrimidin-7-one derivative, is the first orally effective PDE5 inhibitor approved for the treatment of erectile dysfunction. Its advent has spurred significant interest in the development of additional PDE5 inhibitors (Allerton et al., 2006). Herein, the title compound as Sildenafil analog was synthesized and determined by X-ray crystal diffraction in order to find new potent PDE5 inhibitors.

In the molecule (Fig. 1), the dihedral angle between the fluorophenyl and pyrimidinon ring is 75.9 (1)°, and the dihedral angle between the methylphenyl and pyrazole ring is 40.3 (1)°. The atoms O1, N1–N6, C5, C8–C14 and C20 are nearly coplanar, and N6, C21–C23 formed a plane.

In the crystal structure, molecules are linked by weak C—H···π (arene) interactions, which connected H6 to the centroid of atoms C14–19, Cg1, (symmetry code: -x,1/2 + y,1/2 - z). In addition, the crystal structure is stablized by intermolecular N—H···O and intramolecular C—H···N hydrogen-bonding interactions (Fig. 2).

Experimental

To a solution of 4-(3-cyano-5-ethoxycarbonyl-p-tolyl-1H-pyrazolyl) iminophosphorane (1.59 g, 3 mmol) in absolute anhydrous CH₂Cl₂, 4-fluorophenylisocyanate (3 mmol) was added at room temperature. The reaction mixture was left unstirred for 6 h at 273–278 K, whereafter a slight excess of butylamine (3.1 mmol) was added. After that, the reaction mixture was stirred for 6 h, the solution was cooled and the reaction product was recrystallized from EtOH and CH₂Cl₂ to give colorless crystals of the title compound in yield 93%, suitable for X-ray analysis.