Ethylmorpholine → HCID 67460660, compound

HRID 554136Notes

Reaction equation

HRID 554136 reaction equation
[CH:1]1([N:5]2[C:12](=[O:13])[CH2:11][CH2:10][C@H:6]2[C:7]([OH:9])=O)[CH2:4][CH2:3][CH2:2]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N1CCOCC1)C.[Cl:44][C:45]1[C:50]([C:51]([F:54])([F:53])[F:52])=[CH:49][CH:48]=[CH:47][C:46]=1[CH2:55][NH2:56].C(=O)([O-])O.[Na+]>ClCCl>[Cl:44][C:45]1[C:50]([C:51]([F:53])([F:54])[F:52])=[CH:49][CH:48]=[CH:47][C:46]=1[CH2:55][NH:56][C:7](=[O:9])[C@@H:6]1[CH2:10][CH2:11][C:12](=[O:13])[N:5]1[CH:1]1[CH2:2][CH2:3][CH2:4]1

Participants

8

Reactant 6

HCID 7525EthylmorpholineHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 52242072-Chloro-3-(trifluoromethyl)benzylamineHCID 67462914HCID 67462914, compound

Product 1

HCID 67460660HCID 67460660, compoundYield 34.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

1-Cyclobutyl-5-oxoproline (0.238 g, 0.82 mmol) was suspended in dichloromethane (3 ml) and to this was added N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.188 g, 0.98 mmol), 1-Hydroxybenzotriazole (0.132 g, 0.98 mmol), and N-ethyl morpholine (0.313 ml, 2.46 mmol). The mixture was stirred at room temperature for 30 minutes and then {[2-chloro-3-(trifluoromethyl)phenyl]methyl}amine (0.205 g, 0.98 mmol) was added to the mixture and stirring continued for ˜20 hrs at room temperature. The mixture was then diluted with more dichloromethane and treated with saturated aqueous sodium hydrogen carbonate. The dichloromethane layer was separated and the aqueous layer was extracted with 3 further aliquots of dichloromethane. The combined organic extracts were washed with water and then with brine, dried over anhydrous magnesium sulphate and evaporated in vacuo to give the crude product. This was further purified by mass-directed automated HPLC to give pure N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-1-cyclobutyl-5-oxoprolinamide (0.105 g) as a white solid.

Workup

  1. stirringstirring
  2. waitcontinued for ˜20 hrs at room temperature
  3. customThe dichloromethane layer was separated
  4. extractionthe aqueous layer was extracted with 3 further aliquots of dichloromethane
  5. washThe combined organic extracts were washed with water
  6. dry with materialwith brine, dried over anhydrous magnesium sulphate
  7. customevaporated in vacuo
  8. customto give the crude product
  9. customThis was further purified

Sources & evidence

ORD record
ord-b4bc421aa6d941a5808f5d909ca00c87
Source dataset
uspto-grants-2011_11
Patent number
US08048907B2

Reaction notes

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