1,2-Dichloroethane → N-[(2S)-2-({3-[(dipropylamino)carbonyl]-benzoyl}amino)-3-phenylpropyl]-L-alanyl-N1-isobutyl-L-valinamide

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Reaction Steps

3-[(Dipropylamino)carbonyl]benzoic acid, (52 mg, 0.21 mmol) is combined with EDC(40 mg, 0.21 mmol) and HOBT (30 mg, 0.22 mmol) in 2.5 mL of DMF and stirred under nitrogen for 1 h. This solution is then added to a solution of N-[(2S)-2-amino-3-phenylpropyl]-L-alanyl-N1-isobutyl-L-valinamide (0.17 mmol) in 1 mL of DMF. The reaction is continued for 3 days at ambient temperature. It is then quenched with 1 N KH2PO4 and diluted with ethyl acetate. The organic phase is washed with water, 1 N NaHCO3, and brine, and dried over Na2SO4. Concentration and chromatography over silica gel, eluting with 5% methanol in dichloromethane, affords 53 mg (0.087 mmol, 51%) of the title compound. Addition of several drops of deuterated methanol to the compound in deuterated chloroform is necessary. NMR (CDCl3+MeOD) δ 7.79 (br d, 1H), 7.69 (s, 1H), 7.44 (m, 2H), 7.30 (m, 4H), 7.26 (m, obscured by CHCl3), 7.19 (m, 2H), 4.33 (m, 1H), 4.03 (d, J=8 Hz, 1H), 3.5-3.4 (m, 3H), 3.13-3.0 (m, 6H), 2.90 (m, 1H), 2.68 (dd, 1H), 2.0 (m, 1H), 1.8-1.7 (m, 3H), 1.5 (m, 2H), 1.31 (d, J=7 Hz, 3H), 0.99 (t, J=7 Hz, 3H), 0.93-0.86 (overlapping d, 12H), 0.72 (t, J=7 Hz, 3H). MS (FAB) m/z 608 (MH+).

Provenance & Evidence