Cyclopentylacetic acid → 4-[1-benzenesulfonyl-5-(2-cyclopentyl-acetylamino)-1H-pyrrolo[2,3-b]pyridin-4-ylamino]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1257594Notes

Reaction equation

HRID 1257594 reaction equation
[CH:1]1([CH2:6][C:7]([OH:9])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(C(C)C)CC)(C)C.Cl.CN(C)CCCN=C=NCC.[C:31]([O:35][C:36]([N:38]1[CH2:43][CH2:42][CH:41]([NH:44][C:45]2[C:50]([NH2:51])=[CH:49][N:48]=[C:47]3[N:52]([S:55]([C:58]4[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=4)(=[O:57])=[O:56])[CH:53]=[CH:54][C:46]=23)[CH2:40][CH2:39]1)=[O:37])([CH3:34])([CH3:33])[CH3:32]>C(Cl)Cl>[C:31]([O:35][C:36]([N:38]1[CH2:39][CH2:40][CH:41]([NH:44][C:45]2[C:50]([NH:51][C:7](=[O:9])[CH2:6][CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)=[CH:49][N:48]=[C:47]3[N:52]([S:55]([C:58]4[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=4)(=[O:56])=[O:57])[CH:53]=[CH:54][C:46]=23)[CH2:42][CH2:43]1)=[O:37])([CH3:34])([CH3:32])[CH3:33]

Participants

6

Reactant 4

HCID 71606Cyclopentylacetic acidHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 673232814-(5-Amino-1-benzenesulfonyl 1H-pyrrolo[2,3-b]pyridine-4-ylamino)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 673437934-[1-benzenesulfonyl-5-(2-cyclopentyl-acetylamino)-1H-pyrrolo[2,3-b]pyridin-4-ylamino]-piperidine-1-carboxylic acid tert-butyl esterYield 45.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

Cyclopentylacetic acid (0.532 ml, 4.24 mmol), diisopropylethylamine (1.5 ml, 8.50 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.89 g, 4.70 mmol) were added sequentially to a solution of 4-(5-amino-1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidine-1-carboxylic acid tert-butyl ester (2.00 g, 4.00 mmol) in CH2Cl2 (60 ml) at 25° C. The reaction mixture was stirred for 9 h at 25° C., then was partitioned between 1.0 M HCl (125 ml) and CH2Cl2 (125 ml). The organic layer was 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 4-[1-benzenesulfonyl-5-(2-cyclopentyl-acetylamino)-1H-pyrrolo[2,3-b]pyridin-4-ylamino]-piperidine-1-carboxylic acid tert-butyl ester (1.05 g, 40%) as an off-white solid. LCMS (Method G, ESI): RT=1.15 min, m+H=582.5. This material was used in the next step below without additional characterization.

Workup

  1. customwas partitioned between 1.0 M HCl (125 ml) and CH2Cl2 (125 ml)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customPurification of the residue by column chromatography on silica gel (gradient: 0 to 8% CH3OH in CH2Cl2)

Sources & evidence

ORD record
ord-bf3ed90bd4f74a63b9ba3ea37432826a
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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