Diisopropylethylamine → (S)-tert-Butyl 4,4-difluoro-2-(2-(phenylcarbamoyl)-1H-pyrrol-1-ylcarbamoyl)pyrrolidine-1-carboxylate

HRID 525002Notes

Reaction equation

HRID 525002 reaction equation
[NH2:1][N:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[C:7]([NH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:8].[C:16]([O:20][C:21]([N:23]1[CH2:27][C:26]([F:29])([F:28])[CH2:25][C@H:24]1[C:30](O)=[O:31])=[O:22])([CH3:19])([CH3:18])[CH3:17].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>ClCCl.CN(C=O)C>[F:29][C:26]1([F:28])[CH2:27][N:23]([C:21]([O:20][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:22])[C@H:24]([C:30](=[O:31])[NH:1][N:2]2[CH:6]=[CH:5][CH:4]=[C:3]2[C:7](=[O:8])[NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:25]1

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 22977458(2S)-1-[(tert-butoxy)carbonyl]-4,4-difluoropyrrolidine-2-carboxylic acidHCID 709224541-amino-N-phenyl-1H-pyrrole-2-carboxamide

Product 1

HCID 86722022(S)-tert-Butyl 4,4-difluoro-2-(2-(phenylcarbamoyl)-1H-pyrrol-1-ylcarbamoyl)pyrrolidine-1-carboxylateYield 97.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

1-Amino-N-phenyl-1H-pyrrole-2-carboxamide (500 mg, 2.48 mmol), (S)-1-(tert-butoxycarbonyl)-4,4-difluoropyrrolidine-2-carboxylic acid (687 mg, 2.73 mmol), HATU (1.04 g, 2.73 mmol) and diisopropylethylamine (476 μl, 2.73 mmol) were dissolved in a mixture of 6 mL of dichloromethane and 6 mL of DMF and stirred at room temperature overnight. The dichloromethane was removed under vacuum and 25 mL of water were poured over the remaining solution. A precipitated appeared and the suspension was stirred overnight. The solid was filtered and washed with water to furnish 1.05 g (97% yield) of the title compound.

Workup

  1. customThe dichloromethane was removed under vacuum and 25 mL of water
  2. additionwere poured over the remaining solution
  3. stirringthe suspension was stirred overnight
  4. filtrationThe solid was filtered
  5. washwashed with water

Sources & evidence

ORD record
ord-0120fe6bc5ad437a855a4937b34e73e1
Source dataset
uspto-grants-2016_05
Patent number
US09340547B2

Reaction notes

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