Diisopropylethylamine → HCID 86757204, compound

Participants

Reaction Steps

To a mixture of (2S,3R)-1-(2,2-dimethyl-1-oxopropyl)-3-(4-hydroxyphenyl)pyrolidine-2-carboxylic acid (45 mg, 0.15 mmol) and (8R,13R)-13-amino-6,14-dioxo-10,11-dithia-7,15-diazaspiro[4.12]heptadecane-8-carboxylic acid 1,1-dimethylethyl ester hydrochloride 70 mg, 0.15 mmol), prepared in Example 6, in 0.5 mL of DMF was added DIPEA (58 mg, 0.45 mmol) and HBTU (59 mg, 0.15 mmol). The solution was stirred at room temperature for 3 hours and was diluted with water to 3 mL. The resulting white precipitate was collected and was dried over night at reduced pressure to give 98 mg of (8R,13R)-13-[[[1-(2,2-dimethyl-1-oxopropyl)-3-(R)-(4-hydroxyphenyl)-2-(S)-pyrrolidinyl]carbonyl]amino]-6,14-dioxo-10,11-dithia-7,15-diazaspiro[4.12]heptadecane-8-carboxylic acid 1,1-dimethylethyl ester as a white solid. This dried solid was the dissolved in 1 mL of dichloromethane and the solution was treated with 4 N HCl in dioxane (2 mL). The solution was stirred overnight and was concentrated. The residue was purified by reversed phase HPLC (5-95% of acetonitrile containing 0.75% of TFA in water over 40 min linear gradient) to give (8R,13R)-13-[[[1-(2,2-dimethyl-1-oxopropyl)-3(R)-(4-hydroxyphenyl)-2(S)-pyrrolidinyl]carbonyl]amino]-6,14-dioxo-10,11-dithia-7,15-diazaspiro[4.12]heptadecane-8-carboxylic acid as white solid (9 mg). HRMS (M+H): Obs. 635.2543, Calcd. 635.2573.

Provenance & Evidence