Potassium Carbonate → HCID 58180891, compound

Participants

Reaction Steps

4-{[4-[3-cyanoprop-2-en-1-yl]-2-(hydroxymethyl)piperazin-1-yl]carbonyl}-3-fluorobenzonitrile (46 mg, 0.14 mmol, as a mixture of E- and Z-mixtures from Step 2) was combined with 4-(1H-pyrazol-4-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (29 mg, 0.093 mmol, prepared as described in WO 2007/070514 Example 65) in DMF (0.14 mL) and potassium carbonate (0.0414 g, 0.299 mmol) was added. The reaction mixture was stirred overnight. The mixture was then filtered and the filtrate was diluted with EtOAc. This solution was washed with water (thrice), brine; dried over sodium sulfate, decanted and concentrated. The crude was then stirred in 1:1 DCM:TFA (4 mL) for 1 h and the solvent removed in vacuo. The residue was then stirred with 0.2 mL ethylenediamine in 1.5 mL MeOH for 30 min. Preparative HPLC-MS (C18, eluting with a gradient of H2O/MeCN containing 0.15% NH4OH) was used to purify product—a mixture of diastereomers (24 mg, 50%). 1H NMR (400 MHz, DMSO-d6, mixture of diastereomers and rotamers): δ 12.12 (br s, 2H), 8.81, 8.80, 8.78, 8.78 (4s, 2H), 8.68, 8.67 (2s, 2H), 8.37, 8.37, 8.36 (3s, 2H), 7.99-7.91 (m, 2H), 7.80-7.72 (m, 2H), 7.63-7.50 (m, 4H), 6.99-6.95 (m, 2H), 5.07-1.84 (m, 28H); LCMS (M+H)+: 514.2.

Provenance & Evidence