Ethylmorpholine → N-[(2-chloro-4-fluorophenyl)methyl]-1-cyclopentyl-5-oxoprolinamide

HRID 554118Notes

Reaction equation

HRID 554118 reaction equation
[CH:1]1([N:6]2[C:13](=[O:14])[CH2:12][CH2:11][C@H:7]2[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N1CCOCC1)C.[Cl:45][C:46]1[CH:51]=[C:50]([F:52])[CH:49]=[CH:48][C:47]=1[CH2:53][NH2:54].C(=O)([O-])O.[Na+]>ClCCl.CN(C)C=O>[Cl:45][C:46]1[CH:51]=[C:50]([F:52])[CH:49]=[CH:48][C:47]=1[CH2:53][NH:54][C:8](=[O:10])[C@@H:7]1[CH2:11][CH2:12][C:13](=[O:14])[N:6]1[CH:1]1[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

9

Reactant 6

HCID 7525EthylmorpholineHCID 757711-HydroxybenzotriazoleHCID 1399092-Chloro-4-fluorobenzylamineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67459886HCID 67459886, compound

Product 1

HCID 49864819N-[(2-chloro-4-fluorophenyl)methyl]-1-cyclopentyl-5-oxoprolinamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

1-Cyclopentyl-5-oxoproline (0.100 g, 0.51 mmol, prepared as described below) was dissolved in a mixture of dichloromethane (2.5 ml) and dimethylformamide (0.5 ml) and to this were added N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.117 g, 0.61 mmol), 1-hydroxybenzotriazole (0.082 g, 0.61 mmol), and N-ethyl morpholine (0.2 ml, 1.52 mmol). The mixture was stirred for 10 minutes and then [(2-chloro-4-fluorophenyl)methyl]amine (0.097 g, 0.61 mmol) was added and the mixture was stirred overnight. Saturated aqueous sodium hydrogen carbonate (10 ml) was added and the mixture stirred vigorously for 15 minutes. The organic phase was separated with a phase separator and the aqueous phase was washed with further aliquots of dichloromethane (3×10 ml). The organic fractions were combined and dried over magnesium sulphate. The solvent was then evaporated and the residue was purified by mass-directed automated HPLC to give pure N-[(2-chloro-4-fluorophenyl)methyl]-1-cyclopentyl-5-oxoprolinamide.

Workup

  1. stirringthe mixture was stirred overnight
  2. stirringthe mixture stirred vigorously for 15 minutes
  3. customThe organic phase was separated with a phase separator
  4. washthe aqueous phase was washed with further aliquots of dichloromethane (3×10 ml)
  5. dry with materialdried over magnesium sulphate
  6. customThe solvent was then evaporated
  7. customthe residue was purified

Sources & evidence

ORD record
ord-e64ddbff05534b5090e621615cab8685
Source dataset
uspto-grants-2011_11
Patent number
US08048907B2

Reaction notes

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