4-Methylmorpholine → {1-[2-[2-Cyclopropylmethyl-4-(1-methylcarbamoyl-2-naphthalen-2-ylethyl)-piperazin-1-yl]-1-(4-fluorobenzyl)-2-oxo-ethylcarbamoyl]cyclopropyl}-carbamic acid tert-butyl ester

Participants

Reaction Steps

To a solution of 2-{4-[2-amino-3-(4-fluorophenyl)-propionyl]-3-cyclopropylmethyl-2-oxo-piperazin-1-yl}-N-methyl-3-naphthalen-2-yl-propionamide, 18, (62 mg, 0.12 mmol) in DMF (2 mL) are added tert-butoxycarbonylamino-cyclopropanecarboxylic acid (28.5 mg, 0.14 mmol), 1-hydroxybenzotriazole (36 mg, 0.266 mmol), N-methylmorpholine (74 mg, 0.74 mmol) and 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide (29 mg, 0.15 mmol) consecutively. The reaction mixture is stirred for 3 hours, quenched with aqueous NH4Cl and extracted several times with ethyl acetate. The combined extracts are dried over Na2SO4, filtered and concentrated in vacuo to a residue, which is purified over silica gel (CH2Cl2/CH3OH, 13:1) to afford the desired product.

Provenance & Evidence