Sodium 2-methylbutan-2-olate → 1-(3-Benzyloxy-phenyl)-3-(3-methoxymethylene-cyclobutyl)-imidazo[1,5-a]pyrazin-8-ylamine

Participants

Reaction Conditions

Reaction Steps

1-(3-Benzyloxy-phenyl)-8-chloro-3-(3-methoxymethylene-cyclobutyl)-imidazo[1,5-a]pyrazine: To a solution of Ph3PCH2OMeCl (2.6 g, 7.44 mmol) in benzene (37 mL) a solution of sodium tert-amylate (819.0 mg, 7.44 mmol) in benzene (9.0 mL) was added at rt. The dark red solution was allowed to stir at rt for 10 min. at which point a solution of 3-[1-(3-Benzyloxy-phenyl)-8-chloro-imidazo[1,5-a]pyrazin-3-yl]-cyclobutanone in benzene (30.0 mL) was added dropwise at rt. The reaction mixture was then heated to 70° C. for 4 h. The reaction was then quenched with NH4Cl sat. Aq. and extracted with diethyl ether (3×). The organic layers were washed with H2O (1×), brine (1×), dried over Na2SO4, filtered and concentrated in vacuo. Purification via HPFC using a 50 g Jones silica gel column (30% EtOAc:Hex) to yield the desired product as a light yellow solid; 1H NMR (CDCl3, 400 MHz) δ 3.29-3.33 (m, 4H), 3.59 (s, 3H), 3.90 (q, 1H, J=8.2 Hz), 5.14 (s, 2H), 5.93 (s, 1H), 7.26-7.66 (m, 11H); MS (ES) 432.05 (M+1), 434.01 (M+3), 435.02 (M+4).

Provenance & Evidence