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

HRID 1257597Notes

Reaction equation

HRID 1257597 reaction equation
FC(F)(F)C(O)=O.C(OC([N:15]1[CH2:20][CH2:19][CH:18]([NH:21][C:22]2[C:27]([NH:28][C:29](=[O:36])[CH2:30][CH:31]3[CH2:35][CH2:34][CH2:33][CH2:32]3)=[CH:26][N:25]=[C:24]3[N:37]([S:40]([C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=4)(=[O:42])=[O:41])[CH:38]=[CH:39][C:23]=23)[CH2:17][CH2:16]1)=O)(C)(C)C.[C:49](#[N:52])[CH:50]=[CH2:51]>C(Cl)Cl>[C:43]1([S:40]([N:37]2[C:24]3=[N:25][CH:26]=[C:27]([NH:28][C:29](=[O:36])[CH2:30][CH:31]4[CH2:32][CH2:33][CH2:34][CH2:35]4)[C:22]([NH:21][CH:18]4[CH2:19][CH2:20][N:15]([CH2:51][CH2:50][C:49]#[N:52])[CH2:16][CH2:17]4)=[C:23]3[CH:39]=[CH:38]2)(=[O:41])=[O:42])[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7855AcrylonitrileHCID 673437934-[1-benzenesulfonyl-5-(2-cyclopentyl-acetylamino)-1H-pyrrolo[2,3-b]pyridin-4-ylamino]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 67345921N-{1-benzenesulfonyl-4-[1-(2-cyano-ethyl)-piperidin-4-ylamino]-1H-pyrrolo[2,3-b]pyridin-5-yl}-2-cyclopentyl-acetamideYield 158%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-524cedebac4f4b49be04c4576e0c906b
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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