1,2-Dichloroethane → HCID 69002685, compound

Participants

Reaction Conditions

Reaction Steps

N-(tert-butoxycarbonyl)-L-proline (0.20 g, 0.42 mmol) was dissolved in THF (10 mL) and the solution was added with Compound 99 (0.14 g, 0.42 mmol), 1-hydroxybenzotriazole monohydrate (75 mg, 0.54 mmol) and EDC (0.11 g, 0.59 mmol), followed by stirring at 60° C. for 2 hours. After the reaction, the reaction mixture was added with ethyl acetate, washed with saturated aqueous sodium hydrogencarbonate solution and the organic layer was concentrated under reduced pressure. The obtained (S)-(E)-N-2-(4-{4-[2-(1H-indazol-3-yl)vinyl]-3-[(3-methylthiophene-2-carbonyl)amino]benzoyl}piperazine-1-carbonyl)pyrrolidine-1-carboxylic acid tert-butyl ester was dissolved in methanol (5.0 mL) and 4 mol/L hydrogen chloride-methanol solution (1.0 mL) was added thereto, followed by heating under reflux at 60° C. for 2 hours. The reaction mixture was concentrated under reduced pressure and the residue was added with saturated aqueous sodium hydrogencarbonate solution and ethyl acetate and then extracted. The obtained crude product was crystallized from ethanol to obtain Compound 231 (0.14 g, 56%).

Provenance & Evidence