Tetrahydrofuran → 2-(3-Chloro-4-fluorophenyl)-N5-(2-(4,4-difluorocyclohexyl)propan-2-yl)-6,7-dihydropyrazolo[1,5-a]pyrazine-3,5(4H)-dicarboxamide

Participants

Reaction Conditions

Reaction Steps

To a solution of Intermediate 232C (56.0 mg, 0.271 mmol) in toluene (2 mL) was added TEA (0.057 mL, 0.407 mmol), DPPA (0.078 mL, 0.339 mmol) and the reaction mixture heated to 80° C. and stirred for 2 h. The reaction mixture was cooled to RT and to it was added a solution of Intermediate 185B (40 mg, 0.136 mmol) in THF (1 mL) and stirred for 12 h. The reaction mixture was diluted with water (15 mL) and extracted with ethyl acetate (2×20 mL) The combined organic layer was washed with brine, dried over Na2SO4, filtered and the filtrate concentrated. The crude compound was purified by reverse phase preparative HPLC to afford Compound 232 (37 mg, 52%). HPLC retention time 1.70 min. and 1.70 min. (Methods J and K respectively). MS(ES): m/z=498 [M+H]+; 1H NMR (400 MHz, DMSO-d6) ppm 7.85 (dd, J=7.3, 2.3 Hz, 1H), 7.73-7.65 (m, 1H), 7.50-7.43 (m, 1H), 7.35 (br. s., 1H), 7.20 (br. s., 1H), 6.21 (s, 1H), 4.69 (s, 2H), 4.12 (t, J=5.0 Hz, 2H), 3.80 (t, J=5.3 Hz, 2H), 2.20 (t, J=12.0 Hz, 1H), 2.08-1.95 (m, 2H), 1.81-1.58 (m, 4H), 1.30-1.13 (m, 8H).

Provenance & Evidence