Acetonitrile → HCID 58180877, compound

Participants

Reaction Steps

To a solution of 4-piperazin-1-yl-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile hydrochloride (125 mg, 0.211 mmol; from Example 12, Step 2) in DCM (2 mL) was added triethylamine (177 uL, 1.27 mmol) followed by 3-fluoro-4-methoxybenzoyl chloride (80 mg, 0.4 mmol). The reaction was stirred at for 16 hours. 4-Dimethylaminopyridine (5 mg, 0.04 mmol) was added. Acetonitrile (0.30 mL) was added to aid in solubility and additional 3-fluoro-4-methoxybenzoyl chloride (80 mg, 0.4 mmol) was added. When reaction was complete as evidenced by LCMS, solvent was removed in vacuo. The residue was stirred in a mixture of 1:1 DCM:TFA for 1 hour, concentrated, then stirred in MeOH (3 mL) containing ethylenediamine (0.5 mL). Preparative HPLC-MS, eluting with a gradient of MeCN/H2O containing 0.15% NH4OH, was used to purify the product (50 mg, 48%). 1H NMR (400 MHz, d6-dmso): δ 12.12 (br s, 1H), 8.81 (s, 1H), 8.68 (s, 1H), 8.37 (s, 1H), 7.60 (d, 1H), 7.27-7.15 (m, 3H), 6.98 (d, 1H), 4.99 (tt, 1H), 3.86 (s, 3H), 3.57-3.17 (m, 6H), 2.89-2.77 (m, 2H), 2.60-2.32 (m, 4H); LCMS (M+H)+: 489.1.

Provenance & Evidence