Ethylmorpholine → HCID 67460909, compound

HRID 554145Notes

Reaction equation

HRID 554145 reaction equation
[CH3:1][N:2]1[C:9](=[O:10])[CH2:8][CH:7]([CH3:11])[C@H:3]1[C:4]([OH:6])=O.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N1CCOCC1)C.[Cl:42][C:43]1[C:48]([C:49]([F:52])([F:51])[F:50])=[CH:47][CH:46]=[CH:45][C:44]=1[CH2:53][NH2:54]>ClCCl.CN(C)C=O>[Cl:42][C:43]1[C:48]([C:49]([F:51])([F:52])[F:50])=[CH:47][CH:46]=[CH:45][C:44]=1[CH2:53][NH:54][C:4](=[O:6])[C@@H:3]1[CH:7]([CH3:11])[CH2:8][C:9](=[O:10])[N:2]1[CH3:1]

Participants

8

Reactant 5

HCID 7525EthylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 52242072-Chloro-3-(trifluoromethyl)benzylamineHCID 67458673HCID 67458673, compound

Product 1

HCID 67460909HCID 67460909, compoundYield 48.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

1,3-Dimethyl-5-oxoproline (0.620 g, 3.6 mmol, prepared as described below), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.822 g, 4.3 mmol), 1-Hydroxybenzotriazole (0.581 g, 4.3 mmol), N-ethyl morpholine (1.4 ml, 10.8 mmol), and {[2-chloro-3-(trifluoromethyl)phenyl]methyl}amine (0.828 g, 3.96 mmol) were combined in a mixture of dichloromethane (10 ml) and dimethylformamide (5 ml) and stirred under argon overnight. The mixture was then washed sequentially with water (50 ml), 0.5 N aqueous hydrogen chloride (50 ml), water (50 ml), saturated aqueous sodium hydrogen carbonate (50 ml) and water (50 ml). The dichloromethane layer was passed through a hydrophobic frit and evaporated in vacuo to give the crude product. This was further purified by mass-directed automated HPLC (10×0.100 g injections) to give pure N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-1,3-dimethyl-5-oxoprolinamide (0.613 g).

Workup

  1. washThe mixture was then washed sequentially with water (50 ml), 0.5 N aqueous hydrogen chloride (50 ml), water (50 ml), saturated aqueous sodium hydrogen carbonate (50 ml) and water (50 ml)
  2. customevaporated in vacuo
  3. customto give the crude product
  4. customThis was further purified by mass-directed automated HPLC (10×0.100 g injections)

Sources & evidence

ORD record
ord-fd424865795f44ad835b128275534b71
Source dataset
uspto-grants-2011_11
Patent number
US08048907B2

Reaction notes

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