10′-Chloro-3′,4′-dihydro-2′H-spiro­[cyclo­propane-1,7′(6′H)-pyrimido[2,1-a]isoquinolin]-6′-one

Kensuke Okuda; Takashi Hirota; Yuta Nishina; Hiroyuki Ishida

doi:10.1107/S1600536812044261

. 2012 Oct 31;68(Pt 11):o3252. doi: 10.1107/S1600536812044261

10′-Chloro-3′,4′-dihydro-2′H-spiro[cyclopropane-1,7′(6′H)-pyrimido[2,1-a]isoquinolin]-6′-one

Kensuke Okuda ^a,^*, Takashi Hirota ^b, Yuta Nishina ^c, Hiroyuki Ishida ^d,^*

PMCID: PMC3515329 PMID: 23284549

Abstract

In the title compound, C₁₄H₁₃ClN₂O, the fused hydropyrimidine ring adopts an envelope conformation with one of the methylene C atoms at the flap. The three-membered ring is approximately perpendicular to the attached isoquinoline ring system, with a dihedral angle of 89.44 (11)°. In the crystal, molecules are linked by a weak C—H⋯π interaction, forming a helical chain along the c axis.

Related literature

For recent reports on the development of complex heterocyclic skeletons for potential pharmaceutics in one step using the Truce–Smiles rearrangement, see: Okuda et al. (2010 ▶, 2011 ▶). For the synthesis of the title compound, see: Okuda et al. (2012 ▶).

Experimental

Crystal data

C₁₄H₁₃ClN₂O
M _r = 260.72
Orthorhombic,
a = 8.8746 (5) Å
b = 13.3273 (7) Å
c = 9.8331 (6) Å
V = 1163.01 (11) Å³
Z = 4
Mo Kα radiation
μ = 0.32 mm⁻¹
T = 180 K
0.25 × 0.21 × 0.03 mm

Data collection

Rigaku R-AXIS RAPIDII diffractometer
Absorption correction: numerical (NUMABS; Higashi, 1999 ▶) T _min = 0.931, T _max = 0.991
17373 measured reflections
3359 independent reflections
3095 reflections with I > 2σ(I)
R _int = 0.027

Refinement

R[F ² > 2σ(F ²)] = 0.031
wR(F ²) = 0.079
S = 1.05
3359 reflections
163 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.32 e Å⁻³
Δρ_min = −0.15 e Å⁻³
Absolute structure: Flack (1983 ▶), 1571 Friedel pairs
Flack parameter: 0.01 (5)

Data collection: PROCESS-AUTO (Rigaku/MSC, 2004 ▶); cell refinement: PROCESS-AUTO; data reduction: CrystalStructure (Rigaku/MSC, 2004 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009 ▶).

Supplementary Material

Click here for additional data file.^{(23.5KB, cif)}

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812044261/ff2085sup1.cif

e-68-o3252-sup1.cif^{(23.5KB, cif)}

Click here for additional data file.^{(164.8KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812044261/ff2085Isup2.hkl

e-68-o3252-Isup2.hkl^{(164.8KB, hkl)}

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

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

Cg1 is the centroid of the C1/N1/C2–C4/C9 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C12—H12B⋯Cg1ⁱ	0.99	2.72	3.6000 (15)	148

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Symmetry code: (i) Inline graphic .

supplementary crystallographic information

Comment

As an extension of our work to develop complex heterocyclic skeletons as leads for potential pharmaceutical agents (Okuda et al., 2011), we found that tricyclic 5-amino-1,2-dihydrofuro[2,3-c]isoquinolines (Okuda et al., 2010), easily accessible by a one step base-induced Truce-Smiles rearrangement of 2-(3-cyanopropoxy)benzonitriles, showed bronchodilator activity (unpublished results). In the pursuit of more potent analogs, we have explored preparation of additional new ring-fused tetracyclic heterocycles. Herein we report that reaction of 5-amino-7-chloro-1,2-dihydrofuro[2,3-c]isoquinoline with 1,3-dibromopropane in the presence of calcium oxide afforded the title compound (Okuda et al., 2012) via rearrangement instead of the anticipated 10-chloro-2,3,6,7-tetrahydrofuro[2,3-c]imidazo[2,1-a]isoquinoline.

In the title compound, the fused hydropyrimidine N1/C1/N2/C12–C14 ring adopts an envelope conformation with atom C13 at the flap. The isoquinoline C1/N1/C2–C9 ring system is planar with an r.m.s. deviation of 0.044 (1) Å. The three-membered C3/C10/C11 ring is approximately perpendicular to the attached isoquinoline ring system with a dihedral angle of 89.44 (11)°. In the crystal, molecules are linked by a weak C—H···π interaction (Table 1), forming a helical chain along the c axis.

Experimental

The detailed experimental procedure for the synthesis of 10'-chloro-3',4'-dihydro-2'H-spiro[cyclopropane-1,7'(6'H)-pyrimido[2,1-a]isoquinolin]-6'-one (m.p. 424–425 K from n-hexane) from 5-amino-7-chloro-1,2-dihydrofuro[2,3-c]isoquinoline was described in our previous paper (Okuda et al., 2012). Single crystals suitable for X-ray diffraction were obtained from an acetonitrile/water solution. The title compound was dissolved in hot acetonitrile, then water was added dropwise until the solution became turbid. Slow evaporation at room temperature gave the colourless crystals