Potassium Carbonate → (1S,3R)-3-(2-((4-Isopropylpyrimidin-5-yl)methylamino)-5-(trifluoromethyl)pyrimidin-4-ylamino)-2,2-dimethylcyclobutanol

Participants

Reaction Conditions

Reaction Steps

In a round-bottomed flask, (1S,3R)-2,2-dimethyl-3-((2-(methylthio)-5-(trifluoromethyl)pyrimidin-4-yl)amino)cyclobutanol (1.0 equiv.) and 3-chlorobenzoperoxoic acid (2.0 equiv.) were combined in THF (0.5 M). The reaction was stirred at 25° C. for 45 min. The mixture was diluted with ethyl acetate. To this solution was added potassium carbonate (4.0 equiv.). The mixture was stirred at room temperature for 30 min and then filtered. The filtrate was concentrated to afford the crude product. A solution of (1S,3R)-2,2-dimethyl-3-((2-(methylsulfonyl)-5-(trifluoromethyl)pyrimidin-4-yl)amino)cyclobutanol (1.0 equiv.), DIEA (3.0 equiv.) and (4-isopropylpyrimidin-5-yl)methanamine dihydrochloride (1.5 equiv.) were combined in dioxane (0.4 M) and stirred at ambient temperature. Additional dioxane was added to ensure solubility. After 1 h at room temperature, LCMS indicated the presence of some product. After 12 h, the reaction was heated to 75° C. for 6 h. Standard work-up afforded the title compound (39% yield). 1H NMR (400 MHz, DMSO-d6) δ (ppm) 8.97 (s, 1H) 8.32-8.68 (m, 1H) 8.03 (s, 1H) 7.26-7.93 (m, 1H) 6.07 (d, J=7.03 Hz, 1H) 4.79 (m, 1H) 4.54 (br. s., 2H) 3.80-3.96 (m, 1H) 3.37-3.59 (m, 1H) 2.15-2.41 (m, 1H) 2.05 (m, 1H) 1.06-1.24 (m, 6H) 0.67-0.92 (m, 6H); MS(ESI) m/z 411.3[M+1]+.

Provenance & Evidence