Triethylamine → HCID 178454677, compound

Participants

Reaction Steps

77 mg (0.76mmol) of triethylamine, 118 mg (0.76mmol) of HOBT and 289 mg (0.76 mmol) of HBTU were added in sequence at room temperature under nitrogen to a solution of 250 mg (0.69mmol) of (S)-α-amino-N-[(1S,2R,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-2,3-dihydroxypropyl]imidazole-4propionamide and 281 mg (0.76 mmol) of rac-α-[[[1-[(cyclopropylmethoxy)carbonyl]-1-methylethyl]sulfonyl]methyl]hydrocinnamic acid in 20 ml of dimethylformamide. The yellow reaction solution was stirred at room temperature overnight. For the working-up, the reaction solution was evaporated in a high vacuum. The residue was taken up in 40 ml of ethyl acetate and extracted twice with in each case 10 ml of saturated sodium hydrogen carbonate solution and 10 ml of saturated sodium chloride solution. The organic extracts were dried over sodium sulphate and subsequently evaporated under reduced pressure. For purification, the residue (560 mg) was chromatographed on 50 g of silica gel using a 95:5:0.1 mixture of methylene chloride, methanol and pyridine as the eluent. After lyophilization from dioxan/water there were obtained 110 mg of the less polar cyclopropylmethyl 2-[[(R)-2-[[(S)-1-[[(1S,2R,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-2,3-dihydroxypropyl]carbamoyl]-2-imidazol-4-ylethyl]carbamoyl]-3-phenylpropyl]sulfonyl]-2-methylpropionate, MS: 715 (M+H)+, and 142 mg of the more polar epimeric cyclopropylmethyl 2-[[(S)-2-[[(S)-1-[[(1S,2R,3S)-1 -(cyclohexylmethyl)-3-cyclopropyl-2,3-dihydroxypropyl]carbamoyl]-2-imidazol-4-ylethyl]carbamoyl]-3-phenylpropyl]sulfonyl]-2-methylpropionate, MS: 715 (M+H)+, each as a colourless powder.

Provenance & Evidence