1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (2S,4R)-1-(Naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidine-2-carboxylic acid [(S)-2-biphenyl-4-yl-1-[1-(2-cyano-ethyl)-1H-tetrazol-5-yl]-ethyl]-amide

Participants

Reaction Steps

A solution of 520 mg (0.9 mmol) (2S,4R)-1-(Naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidine-2-carboxylic acid and 315 mg (1 mmol) (1S)-3-[5-(1-Amino-2-biphenyl-4-yl-ethyl)-tetrazol-1-yl]-propionitrile [S. De Lombaert. Preparation of tetrazolylalkylaminomethylphosphonates as neutral endopeptidase inhibitors. U.S., 17 pp. CODEN: USXXAM. U.S. Pat. No. 5,273,990 A 931228] in 5 ml THF was cooled to 0° C. and treated with 206 mg (1.1 mmol) EDCI and 14 mg (0.09 mmol) HOBT. The reaction was stirred for 3 h at RT and partitioned between aqueous 10% KHSO4/ethyl acetate (3×). The organic phases were washed with aqueous saturated NaHCO3 solution and dried over Na2SO4. Purification by flash-chromatography on silicagel (Hexane/EtOAc 1:1) gave 639 mg (81%) (2S,4R)-1-(Naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidine-2-carboxylic acid [(S)-2-biphenyl-4-yl-1-[1-(2-cyano-ethyl)- 1H-tetrazol-5-yl]-ethyl]-amide, Mp: 122-133 slow dec, MS: 880 (MH+).

Provenance & Evidence