反应详情

温度

25 °C

Racemic 3-methylpentanoic acid (0.180 ml, 1.4 mmol), HATU (0.53 g, 1.4 mmol), and diisopropylethylamine (0.46 ml, 2.7 mmol), were added sequentially to a solution of 3-[4-(5-amino-1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidin-1-yl]-propionitrile (0.54 g, 1.3 mmol, prepared as described in Example 118) in DMF (20 ml) at 25° C. The reaction mixture was stirred for 4 h at 25° C., then was concentrated under reduced pressure. The residue was partitioned between half-saturated NaHCO3 (100 ml) and EtOAc (2×200 ml). The organic layers were dried over MgSO4, filtered, and the filtrate was concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel (gradient: 0 to 8% CH3OH in CH2Cl2) afforded 3-methyl-pentanoic acid {1-benzenesulfonyl-4-[1-(2-cyano-ethyl)-piperidin-4-ylamino]-1H-pyrrolo[2,3-b]pyridin-5-yl}-amide (0.706 g, 110%) as an off-white solid. LCMS (Method G, ESI): RT=0.73 min, m+H=523.4. This material was used in the next step below without further characterization.

1. concentrationwas concentrated under reduced pressure
2. customThe residue was partitioned between half-saturated NaHCO3 (100 ml) and EtOAc (2×200 ml)
3. dry with materialThe organic layers were dried over MgSO4
4. filtrationfiltered
5. concentrationthe filtrate was concentrated under reduced pressure
6. customPurification of the residue by column chromatography on silica gel (gradient: 0 to 8% CH3OH in CH2Cl2)