Triethylamine → 4-Cyano-2,3-dihydro-indole-1-carboxylic acid 3-(2-methyl-1,2,3,4-tetrahydro-isoquinolin-7-ylcarbamoyl)-benzylamide

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Reaction Conditions

Reaction Steps

To a solution of 2,3-dihydro-1H-indole-4-carbonitrile (25 mg, 0.168 mmol) in acetonitrile (3 ml) add CDI (28 mg, 0.168 mmol) followed by 4-dimethylaminopyridine (DMAP) (42 mg, 0.340 mmol) and stir the sealed vial at 90° C. for 4 h. Concentrate the reaction to dryness and add a solution of 3-aminomethyl-N-(2-methyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-benzamide dihydrochloride (62 mg, 0.17 mmol) and Et3N (0.081 mL, 0.588 mmol) in DMF (3 mL). Stir the sealed vial at 90° C. for 4 h. Dilute the reaction with water (1 mL) and quench with TFA (0.3 mL). Purify this by prep HPLC (10% to 90% CH3CN/water. Pool and concentrate fractions containing product. Suspend the residue in EtOAc (3 mL) and precipitate with hexane (100 mL). Filter washing with hexane to afford the desired product 4-cyano-2,3-dihydro-indole-1-carboxylic acid 3-(2-methyl-1,2,3,4-tetrahydro-isoquinolin-7-ylcarbamoyl)-benzylamide as a solid (12 mg, 0.02 mmol). MS, electrospray 467.1 (M+H), rt 1.22 min.

Provenance & Evidence