Dicyclohexylcarbodiimide → (2R)-2-[N-(4-Chlorobenzenesulfonyl)-N-(cyclopropylcarbamoylmethyl)amino]-4-methyl-pentanoic acid amide

Participants

Reaction Steps

To a solution of {N-[(1R)-1-carbamoyl-3-methyl-butyl]-N-(4-chlorobenzenesulfonyl)amino}acetic acid (Example 59, 175 mg, 0.480 mmol), cyclopropylamine (41 uL, 0.58 mmol) in CH2Cl2 (3 mL) was added 1-hydroxybenzotriazole (47 mg, 0.72 mmol), and 1,3-dicyclohexylcarbodiimide (144 mg, 0.720 mmol). The reaction was stirred for 18 h at rt, and then was poured into an EtOAc/water mixture. The organic layer was separated, dried over MgSO4, and concentrated to a clear oil residue. The residue was further purified by Biotage 40S (eluted in 40% EtOAc in hexanes) to afford a white solid (54 mg, 29%). MS (ESI), (M+H)+ 402.2; 1H NMR (CDCl3, 500 MHz) δ 7.85 (dd, 2H, J=1.9, 8.9), 7.50 (dd, 2H, J=2.0, 8.7), 7.40 (br s, 1H), 6.55 (br s, 1H), 6.30 (br s, 1H), 4.23 (dd, 1H, J=2.9, 8.9), 3.92 (d, 1H, J=17), 3.83 (d, 1H, J=17), 2.68-2.73 (m, 1H), 1.75-1.83 (m, 1H), 1.50-1.57 (m, 1H), 1.40-1.49 (m, 1H), 0.88 (d, 3H, J=6.4), 0.87 (d, 3H, J=6.7), 0.80 (d, 2H, J=7.0), 0.51 (t, 2H, J=4.0).

Provenance & Evidence