Potassium Carbonate → HCID 50995826, compound

Participants

Reaction Steps

Potassium carbonate (0.170 g, 1.23 mmol) was added to a mixture of 4-({(2R)-4-[3-cyanoprop-2-en-1-yl]-2-methylpiperazin-1-yl}carbonyl)-3-fluorobenzonitrile (0.12 g, 0.38 mmol, mixture of E- and Z-isomers from Step 2) and 4-(1H-pyrazol-4-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (0.12 g, 0.38 mmol, prepared as described in WO 2007/070514 Example 65) in DMF (0.59 mL) and the mixture was stirred overnight. The reaction mixture was then filtered and the filtrate was diluted with EtOAc. The filtrate was then washed with water (thrice), followed by brine, dried over sodium sulfate, decanted and concentrated. A portion of the crude product was dissolved in a 1:1 mixture of DCM:TFA, stirred at RT for 1 h, and concentrated. The residue was dissolved in methanol (1 mL) and 0.2 mL of aqueous ammonium hydroxide was added. After stirring for 2 h, the reaction mixture was concentrated. Preparative HPLC-MS (C18, eluting with a gradient of H2O/MeCN containing 0.15% NH4OH) afforded product as a mixture of two diastereomers. 1H NMR (300 MHz, DMSO-d6, diastereomers, rotamers): δ 12.11 (br s, 2H), 8.84-8.79 (m, 2H), 8.68-8.66 (m, 2H), 8.37-8.35 (m, 2H), 8.02-7.93 (m, 2H), 7.80-7.73 (m, 2H), 7.64-7.53 (m, 4H), 6.99-6.94 (m, 2H), 5.07-4.85 (m, 2H), 4.71-4.51 (m, 1H), 4.34 (t, 1H), 3.58-1.94 (m, 20H), 1.19 (d, 1.5H), 1.12 (d, 1.5H), 1.05 (d, 1.5H), 0.94 (d, 1.5H); 19F NMR (300 MHz, DMSO-D6): −114.54 to −115.75 (m, 2F); LCMS (M+H)+: 498.2.

Provenance & Evidence