Ammonia → [1-(4-Amino-pyrimidin-2-yl)-cyclopropyl]-carbamic acid tert-butyl ester

Participants

Reaction Steps

3-Dimethylamino-acrylonitrile (0.05 mL, 0.50 mmol) was dissolved in EtOH (1 mL) and NaOEt solution (21 wt % in EtOH, 0.19 mL, 0.50 mmol) was added. This was stirred for 1 h and then (1-Carbamimidoyl-cyclopropyl)-carbamic acid tert-butyl ester hydrochloride (50 mg, 0.25 mmol) was added. The reaction was stirred for 1.5 h at 60° C. and then solid NH4Cl (27 mg, 0.50 mmol) and NH3 (7 M in MeOH, 0.50 mL, 3.5 mmol) were added and stirring was continued at 60° C. for 1 h and then at 100° C. for 17 h. Additional 3-dimethylamino-acrylonitrile (0.1 mL, 0.87 mmol) was added to the reaction and stirring was continued at 100° C. for 22 h. The solvent was removed under a stream of N2 and the residue was directly purified by reversed phase HPLC (20% MeCN/H2O+0.1% TFA) to give a red semisolid that was neutralized by dissolving in EtOAc (5 mL) and washing with saturated aqueous NaHCO3 (2×5 mL). The organic phase was dried with Na2SO4 and concentrated to give 29 mg of the title compound as a red semisolid, m/z 251.44 [M+1]+.

Provenance & Evidence