4-Methylmorpholine → 3'-Hydroxy-biphenyl-4-carboxylic acid 3-(2-methyl-1,2,3,4-tetrahydro-isoquinolin-7-ylcarbamoyl)-benzylamide

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Reaction Steps

To a vial containing 3′-hydroxy-biphenyl-4-carboxylic acid (26 mg, 0.12 mmol) add a solution of HATU (2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate) (57 mg, 0.15 mmol) in DMF (1 mL) followed by a solution of 3-aminomethyl-N-(2-methyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-benzamide dihydrochloride (37 mg, 0.10 mmol) and 4-methylmorpholine (0.044 mL, 0.40 mmol) in DMF (1 mL). Shake the reaction at rt for 24 h. Concentrate in vacuo to an oil. Dissolve the residue in 10% water in DMSO (0.9 mL) and purify by prep-HPLC (10% to 90%, CH3CN/H2O). Concentrate fractions to afford the desired product 3′-hydroxy-biphenyl-4-carboxylic acid 3-(2-methyl-1,2,3,4-tetrahydro-isoquinolin-7-ylcarbamoyl)-benzylamide as a solid in 45% yield (22 mg, 0.045 mmol). MS, electrospray (M+H) 492.4, rt 2.29 min.

Provenance & Evidence