反应详情

1H-Indazole-5-sulfonyl chloride (26 mg, 0.12 mmol; from Step 1) was added 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 (24 mg, 0.041 mmol; from Example 12, Step 2) and triethylamine (57 uL, 0.40 mmol) in acetonitrile (0.30 mL). The mixture was stirred for 16 hours, then solvent was removed in vacuo. The residue was stirred in a 1:1 mixture of DCM:TFA for 1 hour, concentrated, and stirred in a solution of methanol (1 mL) containing ethylenediamine (0.2 mL) for one hour. Purification via preparative HPLC-MS, eluting with a gradient of MeCN/H2O containing 0.15% NH4OH afforded product as the free base (5 mg, 24%). 1H NMR (300 MHz, d6-dmso): δ 12.08 (br s, 1H), 8.70 (s, 1H), 8.60 (s, 1H), 8.31-8.30 (m, 2H), 8.26-8.23 (m, 1H), 7.72 (d, 1H), 7.61 (dd, 1H), 7.52 (d, 1H), 6.87 (d, 1H), 4.93-4.81 (m, 1H), 3.39-2.41 (m, 12H); LCMS (M+H)+: 517.1.

1. customsolvent was removed in vacuo
2. stirringThe residue was stirred in a 1:1 mixture of DCM
3. waitTFA for 1 hour
4. concentrationconcentrated
5. stirringstirred in a solution of methanol (1 mL)
6. additioncontaining ethylenediamine (0.2 mL) for one hour
7. customPurification via preparative HPLC-MS
8. washeluting with a gradient of MeCN/H2O containing 0.15% NH4OH afforded product as the free base (5 mg, 24%)