(R)-3-Pyrrolidinol → 5-(2,6-Difluoro-phenylmethanesulfonyl)-3-[1-[4-((r)-3-hydroxy-pyrrolidine-1-carbonyl)-3,5-dimethyl-1h-pyrrol-2-yl]-meth-(z)-ylidene]-1,3-dihydro-indol-2-one

HRID 1359886Notes

Reaction equation

HRID 1359886 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[CH2:9][S:10]([C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17](=[O:22])/[C:16]/2=[CH:23]\[C:24]1[NH:28][C:27]([CH3:29])=[C:26]([C:30]([OH:32])=O)[C:25]=1[CH3:33])(=[O:12])=[O:11].[NH:34]1[CH2:38][CH2:37][C@@H:36]([OH:39])[CH2:35]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[CH2:9][S:10]([C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17](=[O:22])/[C:16]/2=[CH:23]\[C:24]1[NH:28][C:27]([CH3:29])=[C:26]([C:30]([N:34]2[CH2:38][CH2:37][C@@H:36]([OH:39])[CH2:35]2)=[O:32])[C:25]=1[CH3:33])(=[O:11])=[O:12]

Participants

5

Reactant 3

HCID 2759337(R)-3-PyrrolidinolHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 697271525-[5-(2,6-difluoro-phenylmethanesulfonyl)-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid

Product 1

HCID 590776125-(2,6-Difluoro-phenylmethanesulfonyl)-3-[1-[4-((r)-3-hydroxy-pyrrolidine-1-carbonyl)-3,5-dimethyl-1h-pyrrol-2-yl]-meth-(z)-ylidene]-1,3-dihydro-indol-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 5-[5-(2,6-difluoro-phenylmethanesulfonyl)-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (236 mg), (R)-pyrrolidin-3-ol (2 eq.), HATU (1.2 eq.) and TEA (0.2 mL) in DMF (3 mL) was stirred at rt for 2 hours. The reaction was concentrated, diluted with DCM, washed with water (2×), sodium carbonate (2×), dried and concentrated. The residue was purified on a silica gel column to give 16 mg of the titled compound as a yellow solid.

Workup

  1. concentrationThe reaction was concentrated
  2. additiondiluted with DCM
  3. washwashed with water (2×), sodium carbonate (2×)
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified on a silica gel column

Sources & evidence

ORD record
ord-7c5ef5066cec4e83a1f9f830fbfc66e5
Source dataset
uspto-grants-2003_07
Patent number
US06599902B2

Reaction notes

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