Ethylmorpholine → N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-5-oxo-1-(phenylmethyl)-D-prolinamide

HRID 554115Notes

Reaction equation

HRID 554115 reaction equation
[O:1]=[C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C@H:5]([C:14]([OH:16])=O)[CH2:4][CH2:3]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N1CCOCC1)C.[Cl:47][C:48]1[C:53]([C:54]([F:57])([F:56])[F:55])=[CH:52][CH:51]=[CH:50][C:49]=1[CH2:58][NH2:59].C(=O)([O-])O.[Na+]>ClCCl.CN(C)C=O>[Cl:47][C:48]1[C:53]([C:54]([F:56])([F:57])[F:55])=[CH:52][CH:51]=[CH:50][C:49]=1[CH2:58][NH:59][C:14](=[O:16])[C@H:5]1[CH2:4][CH2:3][C:2](=[O:1])[N:6]1[CH2:7][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

9

Reactant 6

HCID 7525EthylmorpholineHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 52242072-Chloro-3-(trifluoromethyl)benzylamineHCID 10900113(S)-1-Benzyl-5-carboxy-2-pyrrolidinone

Product 1

HCID 67463195N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-5-oxo-1-(phenylmethyl)-D-prolinamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

5-oxo-1-(phenylmethyl)proline (0.100 g, 0.46 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 (0.105 g, 0.55 mmol), 1-hydroxybenzotriazole (0.074 g, 0.55 mmol), and N-ethyl morpholine (0.143 ml, 1.37 mmol). The mixture was stirred for 10 minutes and then {[2-chloro-3-(trifluoromethyl)phenyl]methyl}amine (0.115 g, 0.55 mmol) was added and the mixture was stirred for 1 hr. 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-3-(trifluoromethyl)phenyl]methyl}-5-oxo-1-(phenylmethyl)-D-prolinamide

Workup

  1. stirringthe mixture was stirred for 1 hr
  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-4d57543c75d9429c9de9930c379d58ce
Source dataset
uspto-grants-2011_11
Patent number
US08048907B2

Reaction notes

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