Trifluoroacetic acid → N-{1-benzenesulfonyl-4-[1-(2-cyano-ethyl)-piperidin-4-ylamino]-1H-pyrrolo[2,3-b]pyridin-5-yl}-2-cyclopentyl-acetamide

Temperatur

25 °C

Trifluoroacetic acid (2 ml) was added to a solution of 4-[1-benzenesulfonyl-5-(2-cyclopentyl-acetylamino)-1H-pyrrolo[2,3-b]pyridin-4-ylamino]-piperidine-1-carboxylic acid tert-butyl ester (0.421 g, 0.724 mmol) in CH2Cl2 (10 ml) at 25° C. The reaction mixture was stirred at 25° C. for 30 min, then was concentrated under reduced pressure. The residue was partitioned between half-saturated NaHCO3 (100 ml) and EtOAc (2×100 ml) and the combined organic layers were dried over MgSO4 and filtered. The filtrate was concentrated under reduced pressure and the residue was dissolved in DMF (8 ml) at 25° C. Acrylonitrile (1.0 ml, 0.200 mmol) was added and the reaction mixture was stirred at 25° C. for 18 h, then was concentrated under reduced pressure. The residue was partitioned between water (100 ml) and EtOAc (2×100 ml). The combined 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 7% CH3OH in CH2Cl2) afforded N-{1-benzenesulfonyl-4-[1-(2-cyano-ethyl)-piperidin-4-ylamino]-1H-pyrrolo[2,3-b]pyridin-5-yl}-2-cyclopentyl-acetamide (0.169 g, 63%) as a white foam. LCMS (Method G, ESI): RT=0.70 min, m+H=535.4. This material was used in the next step below without additional characterization.

1. concentrationwas concentrated under reduced pressure
2. customThe residue was partitioned between half-saturated NaHCO3 (100 ml) and EtOAc (2×100 ml)
3. dry with materialthe combined organic layers were dried over MgSO4
4. filtrationfiltered
5. concentrationThe filtrate was concentrated under reduced pressure
6. dissolutionthe residue was dissolved in DMF (8 ml) at 25° C
7. stirringthe reaction mixture was stirred at 25° C. for 18 h
8. concentrationwas concentrated under reduced pressure
9. customThe residue was partitioned between water (100 ml) and EtOAc (2×100 ml)
10. dry with materialThe combined organic layers were dried over MgSO4
11. filtrationfiltered
12. concentrationthe filtrate was concentrated under reduced pressure
13. customPurification of the residue by column chromatography on silica gel (gradient: 0 to 7% CH3OH in CH2Cl2)

ORD-Eintrag

ord-524cedebac4f4b49be04c4576e0c906b

Quelldatensatz

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08461328B2