Diisopropylethylamine → HCID 70945453, compound

Participants

Reaction Conditions

Reaction Steps

A solution of (R)-3-((3-(methylsulfonyl)phenyl)sulfonyl)-2-(((S)-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl)-amino)propanoic acid (7.3 g; 15 mmol) and HATU (6.84 g; 18.0 mmol; 120 mole %) in anhydrous dichloromethane (200 mL) was stirred at ambient temperature for 5 minutes, then (3S)-3-amino-N-cyclopropyl-2-hydroxypentanamide hydrochloride (35.0 mmol; 233 mole %) was added and the mixture stirred for 5 minutes. The reaction mixture was then cooled to 0-5° C. and treated with the dropwise addition of DIPEA (7.8 mL; 5.8 g; 45 mmol; 300 mol %). After the addition was complete, the cooling bath was removed and the reaction was stirred for 2.5 h at ambient temperature. The reaction mixture was concentrated in vacuo and partitioned between ethyl acetate and water. The layers were separated and the organic phase was washed in sequence with a solution of 10% aqueous potassium hydrogensulfate, water, 10% aqueous sodium bicarbonate, water, and finally saturated aqueous sodium chloride. The organic phase was dried (MgSO4), and concentrated almost to dryness. The residue was triturated with diethyl ether then some hexane was added. The resulting solid was filtered and washed with hexane to give 8.6 g (96%) of (3S)—N-cyclopropyl-2-hydroxy-3-((R)-3-((3-(methylsulfonyl)phenyl)sulfonyl)-2-(((S)-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl)amino)propanamido)pentanamide as an off-white solid. LC-MS, positive ion mode: m/z=638 [M+H]+ (100%); negative ion mode: m/z=636 [M−H]− (100%). Methods for the preparation of starting materials are disclosed in U.S. Pat. No. 7,488,848.

Provenance & Evidence