Dimethylformamide → 5-[2-((2S,4S)-2-cyano-4-fluoro-pyrrolidin-1-yl)-2-oxo-ethylamino]-N,N,5-trimethyl-hexahydro-cyclopenta[c]pyrrole-2(1H)-carboxamide

HRID 1961609Notes

Reaction equation

HRID 1961609 reaction equation
[CH3:1][N:2]([CH3:15])[C:3]([N:5]1[CH2:9][CH:8]2[CH2:10][C:11]([NH2:14])([CH3:13])[CH2:12][CH:7]2[CH2:6]1)=[O:4].Cl[CH2:17][C:18]([N:20]1[CH2:24][C@@H:23]([F:25])[CH2:22][C@H:21]1[C:26]#[N:27])=[O:19].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>ClCCl>[CH3:15][N:2]([CH3:1])[C:3]([N:5]1[CH2:9][CH:8]2[CH2:10][C:11]([NH:14][CH2:17][C:18]([N:20]3[CH2:24][C@@H:23]([F:25])[CH2:22][C@H:21]3[C:26]#[N:27])=[O:19])([CH3:13])[CH2:12][CH:7]2[CH2:6]1)=[O:4]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 57518632(2S,4S)-1-(2-Chloroacetyl)-4-fluoropyrrolidine-2-carbonitrileHCID 686275765-Amino-5-methyl-hexahydro-cyclopenta[c]pyrrole-2-carboxylic acid dimethylamide

Product 1

HCID 687768935-[2-((2S,4S)-2-cyano-4-fluoro-pyrrolidin-1-yl)-2-oxo-ethylamino]-N,N,5-trimethyl-hexahydro-cyclopenta[c]pyrrole-2(1H)-carboxamideYield 50.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-Amino-5-methyl-hexahydro-cyclopenta[c]pyrrole-2-carboxylic acid dimethylamide 11c (1.3 g, 7.58 mmol), (2S,4S)-1-(2-chloroacetyl)-4-fluoropyrrolidine-2-carbonitrile 13g (1.74 g, 9.1 mmol), potassium carbonate (1.26 g, 9.1 mmol), 30 mL of N,N-dimethylformamide and 18 mL of dichloromethane were added to a flask under nitrogen atmosphere. The reaction mixture was reacted for overnight at 30° C. upon heating by an oil bath. The reaction was monitored by TLC until the disappearance of the starting materials. The mixture was concentrated to remove N,N-dimethylformamide. The resulting residue was purified by silica gel column chromatography to obtain the title compound 5-[2-((2S,4S)-2-cyano-4-fluoro-pyrrolidin-1-yl)-2-oxo-ethylamino]-5-methyl-hexahydro-cyclopenta[c]pyrrole-2-carboxylic acid dimethylamide 18a (1.39 g, yield 50%) as a white solid.

Workup

  1. customThe reaction mixture was reacted for overnight at 30° C.
  2. temperatureupon heating by an oil bath
  3. concentrationThe mixture was concentrated
  4. customto remove N,N-dimethylformamide
  5. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-ef49cdc4ab7346b2be4e1ef286aa8f0d
Source dataset
uspto-grants-2013_04
Patent number
US08415349B2

Reaction notes

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