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To a stirred solution of (2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxy-pyrrolidine-2-carboxylic acid (3.59 g, 15.52 mmol) in 65 mL of DMSO was added NaOtBu (2.86 g, 29.75 mmol) at 0 C. and the mixture was stirred at room temperature for 2 h. To the mixture was added 4-chloro-2-(4-isopropoxyphenyl)benzofuro[3,2-d]pyrimidine (4.38 g, 12.93 mmol) and 65 mL DMSO. The mixture was stirred at room temperature for 1 h. The mixture was poured into ice water, treated with 6N HCl aqueous solution to adjust pH to ~3, and extracted with ethyl acetate. The ethyl acetate layer was washed with water and then brine, dried over MgSO4 and concentrated in vacuo to give 6.91 g of (2S,4R)-1-(tert-butoxycarbonyl)-4-(2-(4-isopropoxyphenyl)benzofuro[3,2-d]pyrimidin-4-yloxy)pyrrolidine-2-carboxylic acid. LC-MS (M+H): 534.2.
(1R,2S)-1-amino-N-(cyclopropylsulfonyl)-2-vinylcyclopropanecarboxamide hydrochloride[ No CAS ]
[ 1315326-78-3 ]
[ 1315326-79-4 ]
Yield
Reaction Conditions
Operation in experiment
With 4-methyl-morpholine; benzotriazol-1-ol; HATU; In dichloromethane; at 0 - 20℃; for 6h;
A mixture of (2S,4R)-1-(tert-butoxycarbonyl)-4-(2-(4-(trifluoromethyl)-phenyl)benzofuro[3,2-d]pyrimidin-4-yloxy)pyrrolidine-2-carboxylic acid (59.3 g, 109.2 mmol), NMM (42.0 mL, 382.2 mmol), HATU (83.0 g, 218.4 mmol), HOBt (4.5 g, 33.0 mmol) and hydrochloride salt of (1R,2S)-1-amino-N-(cyclopropylsulfonyl)-2-vinylcyclopropanecarboxamide (37.7 g, 163.8 mmol) in 546 mL of dry methylene chloride was stirred at room temperature for 3 h. To the mixture was added 600 mL of methylene chloride. The mixture was stirred for 1 h and filtered to move the solid. The methylene chloride solution was extracted thrice with saturated NH4Cl aqueous solution, dried over MgSO4 and concentrated in vacuo. To the crude compound was added 800 mL of methylene chloride. The mixture was filtered to give 46.8 g of the Boc-protected compound. LC-MS (M+H): 756.2.