4-Methylmorpholine → 1-Isopropyl-6-methyl-4-oxo-5-(3-trifluoromethyl-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid 3-fluoro-4-methanesulfonyl-benzylamide

HRID 524350Notes

Reaction equation

HRID 524350 reaction equation
[CH:1]([N:4]1[C:9]([CH3:10])=[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)[C:7](=[O:21])[C:6]([C:22]([OH:24])=O)=[CH:5]1)([CH3:3])[CH3:2].[F:25][C:26]1[CH:27]=[C:28]([CH:31]=[CH:32][C:33]=1[S:34]([CH3:37])(=[O:36])=[O:35])[CH2:29][NH2:30].CN1CCOCC1.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.C(OCC)(=O)C>ClCCl>[F:25][C:26]1[CH:27]=[C:28]([CH:31]=[CH:32][C:33]=1[S:34]([CH3:37])(=[O:36])=[O:35])[CH2:29][NH:30][C:22]([C:6]1[C:7](=[O:21])[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:19])([F:18])[F:20])[CH:12]=2)=[C:9]([CH3:10])[N:4]([CH:1]([CH3:2])[CH3:3])[CH:5]=1)=[O:24]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 8857Ethyl AcetateHCID 111923Propylphosphonic anhydrideHCID 69381849HCID 69381849, compoundHCID 867115961-Isopropyl-6-methyl-4-oxo-5-(3-trifluoromethyl-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid

Product 1

HCID 732968561-Isopropyl-6-methyl-4-oxo-5-(3-trifluoromethyl-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid 3-fluoro-4-methanesulfonyl-benzylamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-isopropyl-6-methyl-4-oxo-5-(3-trifluoromethyl-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid (preparation 3, 60 mg, 0.177 mmol), preparation 32b (72 mg, 0.354 mmol), N-methylmorpholine (0.10 mL, 0.910 mmol) in dichloromethane (1 mL) is added at 0° C. 1-propanephosphonic acid cyclic anhydride in ethyl acetate (0.31 mL, 50%, 0.53 mmol). The reaction mixture is stirred for 18 h at room temperature. The volatiles are evaporated under reduced pressure and the remaining residue is purified by preparative reversed-phase HPLC (Sunfire, gradient of acetonitrile in water, 0.1% TFA, 60° C.). Yield: 24 mg (26% of theory); ESI mass spectrum: [M+H]+=525; Retention time HPLC: 0.86 min (005_CA01).

Workup

  1. additionis added at 0° C
  2. customThe volatiles are evaporated under reduced pressure
  3. customthe remaining residue is purified by preparative reversed-phase HPLC (Sunfire, gradient of acetonitrile in water, 0.1% TFA, 60° C.)
  4. custom0.86 min (005_CA01)

Sources & evidence

ORD record
ord-aa6c15017a954b13ad5fc9fdbd756b81
Source dataset
uspto-grants-2016_05
Patent number
US09340507B2

Reaction notes

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