Hydrochloric Acid → HCID 67229334, compound

Participants

Reaction Steps

Prepared as described in example 24 using 2-chloro-6-(trifluoromethyl)pyridine in place of 4-chloro-6-(trifluoromethyl)pyrimidine and modifying step 9 as follows. To a solution of HCl salt of 1,5-anhydro-2,3-dideoxy-3-{[(1R,3S)-3-{[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl]carbonyl}-3-(2,2-difluoroethyl)cyclopentyl]amino}-4-O-methyl-D-erythro-pentitol (183 mg, 0.43 mmol) in DMSO (2 ml) was added triethylamine (0.2 ml, 1.43 mmol) and 2-chloro-6-(trifluoromethyl)pyridine (179 mg, 1.05 mmol). The reaction was healed to 120° C. for 14.5 hours. The reaction was cooled to room temperature, and added to stirring ice water. The mixture was extracted with ethyl acetate (3x). The combined organics were washed with brine, dried over MgSO4 concentrated under reduced pressure and purified with the Biotage (0-100% methanol/ethyl acetate, 15 column volumes) to give 1,5-anhydro-2,3-dideoxy-3-{[(1R,3S)-3-(2,2-difluoroethyl)-3-({(1S,4S)-5-[6-(trifluoromethyl)pyridin-2-yl]-2,5-diazabicyclo[2.2.1]hept-2-yl}carbonyl)cyclopentyl]amino}-4-O-methyl-D-erythro-pentitol as a brown foam (58 mg 28%). LC/MS (M+H)=533.2551 exp, 533.2546 obs; 1H NMR (400 MHz, CDCl3) δ ppm 7.54-7.51 (1H), 6.91-6.89 (1H), 6.51-6.38 (1H), 5.94-5.54 (1H), 5.11-4.70 (2H), 4.06-4.01 (1H), 3.93-3.87 (1H), 3.70-3.53 (2H), 3.51-3.31 (6H), 3.27-3.20 (3H), 2.78-2.61 (1H), 2.53-2.36 (1H), 2.20-1.80 (7H), 1.68-1.38 (5H)

Provenance & Evidence