Tetrahydrofuran → 2-(3-Chloro-4-fluorophenyl)-N5-(1-(cyanomethyl)cyclobutyl)-6,7-dihydro pyrazolo[1,5-a]pyrazine-3,5(4H)-dicarboxamide

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of Intermediate 220C (0.020 g, 0.145 mmol) in toluene (0.5 mL) was added TEA (0.081 mL, 0.578 mmol), DPPA (0.078 mL, 0.361 mmol) and the reaction mixture was warmed to 90° C. and stirred for 2 h. The reaction mixture was cooled to RT and to it was added a solution of Intermediate 185B (0.040 g, 0.145 mmol) in THF (0.5 mL) and stirred at RT for 16 h. The reaction mixture was quenched with a 10% aqueous solution of NaHCO3 and extracted with EtOAc (3×10 mL) The combined organic layer was washed with water, dried over Na2SO4, filtered and the filtrate concentrated. The crude product was purified by preparative HPLC to afford Compound 220 as a pale yellow solid (20 mg, 32%). HPLC retention times 1.21 min. and 1.21 min. (Method E and L respectively). MS(ES): m/z=431 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.85 (dd, J=7.28, 2.26 Hz, 1H), 7.66-7.71 (m, 1H), 7.46 (t, J=9.04 Hz, 1H), 7.34 (br. s., 1H), 7.29 (s, 1H), 7.18 (br. s., 1H), 4.74 (s, 2H), 4.14 (t, J=5.27 Hz, 2H), 3.86 (t, J=5.27 Hz, 2H), 3.11 (s, 2H), 2.17-2.27 (m, 2H), 2.02-2.11 (m, 2H), 1.78-1.91 (m, 2H).

Provenance & Evidence