Acetic Acid → N-[(2S)-2-({3-[(dipropylamino)carbonyl]benzoyl}amino)-4-methylpentyl]-L-alanyl-N1-isobutyl-L-valinamide

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Reaction Steps

(290 mg, 0.84 mmol) in 6 mL of dry THF is added to L-alanyl-N1-isobutyl-L-valinamide (EXAMPLE 1, 205 mg, 0.84 mmol) under nitrogen. To this is added 0.12 mL of acetic acid and sodium triacetoxyborohydride (300 mg, 1.41 mmol), and the mixture is stirred for 3 days. Methanol (1 mL) is added. And the mixture is stirred for 3 more hours. It is diluted with 150 mL of ethyl acetate and 5 mL of methanol, and the organic phase is washed successively with 15 mL of 1 N NaHCO3, water, and brine. The solution is dried with Na2SO4, concentrated, and chromatographed over silica gel. Elution with 4% methanol in dichloromethane, followed by 8% methanol in dichloromethane, afforded the title compound as a white solid (154 mg, 0.27 mmol, 32%). 1H NMR (CDCl3) δ 7.88 (m, 1H), 7.78 (m, 2H), 7.44 (m, 2H), 7.00 (d, J=8 Hz, 1H), 6.69 (br t, J=6 Hz, 1H), 4.14 (dd, J=7, 9 Hz, 1H), 4.04 (m, 1H), 3.46 (m, 2H), 3.16-3.04 (m, 5H), 2.87 (m, 1H), 2.64 (dd, J=4, 13 Hz, 1H), 2.03 (m, 1H), 1.75-1.63 (m, 5H), 1.53 (m, 2H), 1.39 (m, 1H), 1.30 (d, J=7 Hz, 3H), 1.0-0.83 (m, 21H), 0.74 (br t, J=7 Hz, 3H). HRMS (ESI) calcd for C32H55N5O4+H1 574.4332, found 574.4332.

Provenance & Evidence