Hydrochloric Acid → HCID 25206610, compound

Participants

Reaction Steps

Added to a solution of 150 mg of 7-(2-oxazolyl)-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxylic acid in 4 cm3 of anhydrous dimethylformamide and under an argon atmosphere are 0.19 cm3 of triethylamine and 201 mg of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)butan-2-ol hydrochloride then 69 mg of 1-hydroxy-7-azabenzotriazole and 97 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. The solution is kept stirring for 15 h at a temperature close to 20° C. 50 cm3 of water and 50 cm3 of ethyl acetate are added to the reaction medium. After decanting, the organic phase is washed with 50 cm3 of a saturated aqueous solution of ammonium chloride, two lots of 20 cm3 of water and 20 cm3 of a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated to dryness under reduced pressure (5 kPa). The residual solution (around 3 cm3) is filtered through a pellet of 15 g of 40-63 μm silica. The silica pellet is washed with 40 cm3 of ethyl acetate. The filtrate is concentrated to dryness under reduced pressure (5 kPa). 255 mg is obtained of a white powder which is dissolved in 10 cm3 of ethyl ether. Added thereto, while stirring, is 0.2 cm3 of a 4N solution of hydrochloric acid in dioxane at a temperature of 20° C. The reaction mixture precipitates. The precipitate is filtered, washed with two lots of 5 cm3 of isopropyl ether and dried under vacuum at a temperature of 35° C. 236 mg of N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)propyl]-7-(2-oxazolyl)-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxamide hydrochloride are obtained in the form of white crystals.

Provenance & Evidence