Trifluoroacetic acid → HCID 118006437, compound

Participants

Reaction Conditions

Reaction Steps

A mixture containing tert-butyl 3-((4-chloro-2-methyl-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(hydroxy)(1-methyl-1H-1,2,3-triazol-5-yl)methyl)azetidine-1-carboxylate (250 mg, 0.42 mmol, Example 31) and trifluoroacetic acid (0.32 mL, 0.32 mmol) in dichloromethane (2 mL) was stirred at 23° C. After 18 hours, dichloromethane (50 mL) and saturated aqueous sodium bicarbonate solution (25 mL) were added. The biphasic mixture was stirred for 5 minutes. The layers were separated. The organic layer was dried with sodium sulfate and the dried solution was filtered. The filtrate was concentrated to provide a residue. This residue was used in the next step without further purification. A mixture of the residue (174 mg), triethylamine (0.25 mL), and acetic anhydride (0.14 mL) in dichloromethane (3.5 mL) was stirred at 46° C. After 2 hours, the flask was cooled to 23° C. Dichloromethane (40 mL) and saturated aqueous sodium bicarbonate solution (25 mL) were added. The biphasic mixture was stirred for 10 minutes at 23° C. The layers were separated. The organic layer was dried with sodium sulfate and the dried solution was filtered. Celite® (3 g) was added to the filtrate and the mixture was concentrated in vacuo. The dry solid was loaded onto a silica gel column for flash-column chromatography. Elution with 100% dichloromethane initially, grading to 5% methanol-dichloromethane provided the title compound as an off-white solid. 1H NMR (500 MHz, CDCl3, 3:1 mixture of amide rotamers, asterisk denotes minor rotamer) δ ppm 8.44 (d, J=2.0 Hz, 1H), 8.38* (d, J=2.1 Hz, 1H), 8.00-7.94 (m, 1H), 7.60-7.51 (m, 3H), 7.48-7.42 (m, 1H), 7.25-7.20 (m, 2H), 6.23 (s, 1H), 5.09* (s, 1H), 4.54-4.45 (m, 2H), 4.43-4.36* (m, 1H), 4.34-4.28* (m, 1H), 4.27-4.19 (m, 1H), 4.19-4.13 (m, 1H), 4.08-3.96 (m, 1H), 3.80-3.65 (m, 4H), 3.63-3.54* (m, 1H), 3.54-3.46 (m, 1H), 2.69-2.63 (m, 3H), 1.82* (s, 3H), 1.65-1.54 (m, overlap with water, 3H); MS (ESI): mass calcd. for C27H25ClF3N5O2, 543.2. m/z found, 544.1 [M+H]+.

Provenance & Evidence