Trimethyl orthoformate → 1-({4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2h-pyran-4-yl}methyl)-1h-imidazo[4,5-c]pyridine

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Reaction Steps

N*4*-{4-[4-(3-Pyrrolidin-1-yl-propoxy)-phenyl]-tetrahydro-pyran-4-ylmethyl}-pyridine-3,4-diamine (280 mg, 0.68 mmol), trimethylorthoformate (5 mL) and formic acid (0.5 mL) were stirred at 40° C. for 18 hours then at 60° C. for 24 hours, then at 80° C. for 24 hours. The reaction mixture was concentrated in vacuo and the residue partitioned between 2M NaOH (30 mL) and DCM (2×30 mL). The organics were combined, dried over sodium sulphate, filtered and concentrated in vacuo to give a brown oil. The crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (95:5:0.5 to 90:10:1 by volume) to provide the title compound as a clear viscous oil (185 mg, 65%). 1H NMR (400 MHz, CDCl3) δ 1.78-1.82 (m, 4H), 1.91-2.03 (m, 4H), 2.15-2.20 (m, 2H), 2.52 (m, 4H), 2.61 (t, 2H), 3.44 (m, 2H), 3.82 (m, 2H), 4.00 (t, 2H), 4.19 (s, 2H), 6.82 (d, 2H), 6.86-6.93 (m, 3H), 7.08 (s, 1H), 8.30 (d, 1H), 9.01 (s, 1H). HRMS ESI+ m/z 421.2590 [MH]+.

Provenance & Evidence