Diisopropylethylamine → 4-[1-benzenesulfonyl-5-(3-benzyloxycarbonylamino-2,2-difluoro-propionylamino)-1H-pyrrolo[2,3-b]pyridin-4-ylamino]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1257637Notes

Reaction equation

HRID 1257637 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[C:20]([NH2:21])=[CH:19][N:18]=[C:17]3[N:22]([S:25]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)(=[O:27])=[O:26])[CH:23]=[CH:24][C:16]=23)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:34]([O:41][C:42]([NH:44][CH2:45][C:46]([F:51])([F:50])[C:47](O)=[O:48])=[O:43])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[NH3:8].[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([NH:14][C:15]2[C:20]([NH:21][C:47](=[O:48])[C:46]([F:51])([F:50])[CH2:45][NH:44][C:42]([O:41][CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[O:43])=[CH:19][N:18]=[C:17]3[N:22]([S:25]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)(=[O:26])=[O:27])[CH:23]=[CH:24][C:16]=23)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 226353073-Benzyloxycarbonylamino-2,2-difluoropropionic acidHCID 673232814-(5-Amino-1-benzenesulfonyl 1H-pyrrolo[2,3-b]pyridine-4-ylamino)-piperidine-1-carboxylic acid tert-butyl ester

Product 2

HCID 222AmmoniaYield 0%HCID 673530054-[1-benzenesulfonyl-5-(3-benzyloxycarbonylamino-2,2-difluoro-propionylamino)-1H-pyrrolo[2,3-b]pyridin-4-ylamino]-piperidine-1-carboxylic acid tert-butyl esterYield 317.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-(5-amino-1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-piperidine-1-carboxylic acid tert-butyl ester (500 mg, 1.06 mmol), 3-benzyloxycarbonylamino-2,2-difluoro-propionic acid (300 mg, 1.15 mmol), diisopropylethylamine (363 μL, 2.12 mmol) and HATU (440 mg, 1.15 mmol) in DCM (10 mL) was stirred at ambient temperature for 3.5 hours. The reaction mixture was concentrated under vacuum and the residue purified by column chromatography on silica gel (gradient: 0 to 5% methanol in DCM then 0 to 10% 2M NH3 in methanol solution in DCM) to afford 1.20 g of 4-[1-benzenesulfonyl-5-(3-benzyloxycarbonylamino-2,2-difluoro-propionylamino)-1H-pyrrolo[2,3-b]pyridin-4-ylamino]-piperidine-1-carboxylic acid tert-butyl ester. LCMS (Method B, ESI): RT=3.91 min, m+H=713.

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. customthe residue purified by column chromatography on silica gel (gradient

Sources & evidence

ORD record
ord-51809884b7f44ca5aef39fd81485828c
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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