O-Phenylenediamine → 2-{4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}-1H-benzimidazole

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carboxylic acid (400 mg, 1.20 mmol), 1,2-diaminobenzene (129 mg, 1.20 mmol) and polyphosphoric acid (2 g) was heated at 130° C. for 2 days. The cooled reaction mixture was partitioned between dichloromethane (20 ml) and aqueous ammonia (20 ml). The aqueous layer was further extracted with dichloromethane (2×50 ml). The organic layers were combined, dried over sodium sulphate, filtered and concentrated in vacuo. The crude product was purified by preparative HPLC on Fraction-Lynx® eluting with water:acetonitrile:TFA (95:5:0.1) to provide the title compound (3.5 mg, 1%). 1H NMR (400 MHz, CDCl3) δ 1.92-1.96 (m, 2H), 2.06-2.21 (m, 4H), 2.40-2.46 (m, 2H), 2.96-3.00 (m, 4H), 3.05-3.09 (m, 2H), 3.16-3.20 (m, 2H), 3.57-3.65 (m, 4H), 3.93 (d, 2H), 5.45 (d, 2H), 7.06 (d, 2H), 7.45 (d, 2H), 7.71-7.74 (m, 2H). LCMS ESI+ m/z 406 [MH]+.

Provenance & Evidence