Ethylmorpholine → N-[(2-chloro-4-fluorophenyl)methyl]-5-oxo-1-phenyl-prolinamide

HRID 554074Notes

Reaction equation

HRID 554074 reaction equation
[O:1]=[C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C@H:5]([C:13]([OH:15])=O)[CH2:4][CH2:3]1.ON1C2C=CC=CC=2N=N1.[Cl:26][C:27]1[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:28]=1[CH2:34][NH2:35].C(N1CCOCC1)C.Cl.CN(C)CCCN=C=NCC>ClCCl.CN(C)C=O>[Cl:26][C:27]1[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:28]=1[CH2:34][NH:35][C:13](=[O:15])[C@@H:5]1[CH2:4][CH2:3][C:2](=[O:1])[N:6]1[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

8

Reactant 5

HCID 7525EthylmorpholineHCID 757711-HydroxybenzotriazoleHCID 1399092-Chloro-4-fluorobenzylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 42260557HCID 42260557, compound

Product 1

HCID 49864874N-[(2-chloro-4-fluorophenyl)methyl]-5-oxo-1-phenyl-prolinamideYield 40.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

5-oxo-1-phenyl-proline (0.047 g, 0.23 mmol, prepared as described below) was dissolved in dichloromethane (˜2 ml) and dimethylformamide (1 ml) and to this was added 1-hydroxybenzotriazole (0.034 g, 0.25 mmol), [(2-chloro-4-fluorophenyl)methyl]amine (0.040 g, 0.25 mmol), N-ethyl morpholine (0.032 ml, 0.25 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.048 g, 0.25 mmol). The mixture was stirred at room temperature for 4.5 hrs. The mixture was diluted with more dichloromethane and washed sequentially with 2M aqueous hydrogen chloride and saturated aqueous sodium hydrogen carbonate. The organic layer was filtered through a phase separator and then evaporated to give the crude product. The crude material was purified by mass-directed automated HPLC to give pure N-[(2-chloro-4-fluorophenyl)methyl]-5-oxo-1-phenyl-prolinamide (0.032 g) as a white solid. LC/MS [M+H]+=347.1, retention time=2.51 minutes.

Workup

  1. washwashed sequentially with 2M aqueous hydrogen chloride and saturated aqueous sodium hydrogen carbonate
  2. filtrationThe organic layer was filtered through a phase separator
  3. customevaporated
  4. customto give the crude product
  5. customThe crude material was purified

Sources & evidence

ORD record
ord-a5c3771b887d4aa99178c2fb2f268c4d
Source dataset
uspto-grants-2011_11
Patent number
US08048907B2

Reaction notes

Loading…