Triethylamine → 2-(Azetidin-1-ylcarbonyl)-5-bromopyrimidine

Participants

Reaction Steps

Oxalyl chloride (1.50 mL, 16.8 mmol) then DMF (2 drops) were added to a mixture of 5-bromopyrimidine-2-carboxylic acid (prepared according to literature procedure described in WO 2005/028452) (2.86 g, 14.0 mmol) in DCM (40 mL). The reaction mixture was stirred at RT for 2 hours, the volatiles removed in vacuo and the residue dissolved in DCM (40 mL). Azetidine hydrochloride (1.44 g, 15.4 mmol) followed by triethylamine (4.29 mL, 30.8 mmol) were added and the mixture stirred at RT for 72 hours. The mixture was concentrated in vacuo and ethyl acetate (100 mL) added to the residue. The organics were washed with water (100 mL), citric acid solution (50 mL), saturated sodium bicarbonate solution (50 mL), brine (50 mL), dried (MgSO4), filtered and the solvent removed in vacuo to give a yellow solid which was chromatographed on silica, eluting with a gradient of 50-100% ethyl acetate in isohexane, to give the desired compound (0.86 g). 1H NMR δ (CDCl3): 2.39 (quin, 2H), 4.32 (t, 2H), 4.63 (t, 2H), 8.92 (s, 2H); m/z 242, 244 (M+H)+

Provenance & Evidence