Water → Ethyl 4-oxo-1-((3'-(trifluoromethyl)biphenyl-2-yl)methyl)-1,4-dihydro-1,5-naphthyridine-3-carboxylate

HRID 1497691Notes

Reaction equation

HRID 1497691 reaction equation
C[N:2]([CH3:19])/[CH:3]=[C:4](/[C:10](=[O:18])[C:11]1[C:16](F)=[CH:15][CH:14]=[CH:13][N:12]=1)\[C:5]([O:7][CH2:8][CH3:9])=[O:6].P([O-])([O-])([O-])=O.[K+].[K+].[K+].[F:28][C:29]([F:45])([F:44])[C:30]1[CH:31]=[C:32]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=2CN)[CH:33]=[CH:34][CH:35]=1.O>CC(N(C)C)=O>[O:18]=[C:10]1[C:11]2[C:16](=[CH:15][CH:14]=[CH:13][N:12]=2)[N:2]([CH2:19][C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=2[C:32]2[CH:33]=[CH:34][CH:35]=[C:30]([C:29]([F:28])([F:45])[F:44])[CH:31]=2)[CH:3]=[C:4]1[C:5]([O:7][CH2:8][CH3:9])=[O:6]

Participants

6

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 1392263[3'-(Trifluoromethyl)[1,1'-biphenyl]-2-yl]-methanamineHCID 86725445(Z)-Ethyl 3-(dimethylamino)-2-(3-fluoropicolinoyl)acrylate

Product 1

HCID 86725446Ethyl 4-oxo-1-((3'-(trifluoromethyl)biphenyl-2-yl)methyl)-1,4-dihydro-1,5-naphthyridine-3-carboxylateYield 37.1%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
74 °C

Procedure

To a brown solution of (Z)-ethyl 3-(dimethylamino)-2-(3-fluoropicolinoyl)acrylate (31) (200 mg, 0.751 mmol) in DMA (dimethylacetamide) (8 mL) in a 20 mL vial were added a solid powder of tribasic potassium phosphate (399 mg, 1.88 mmol) and (3′-(trifluoromethyl)biphenyl-2-yl)methanamine (208 mg, 0.826 mmol) at room temperature under a nitrogen atmosphere. The resulting brown suspension was heated to 74° C. and stirred for 15 h at which time LCMS analysis indicated the absence of starting material. Then, it was cooled to room temperature and poured slowly into water (100 mL), but no solids precipitated. Then, the organic compound was extracted with dichloromethane and the combined extracts were washed with water and brine solution, and dried over anhydrous MgSO4. Filtration and concentration gave the crude brown oil which was purified using ISCO (120 g) column chromatography, eluting with ethyl acetate in hexanes (0 to 100%) and then 5 to 10% methanol in dichloromethane. The desired fractions were combined and the solvent was removed under vacuum to obtain ethyl 4-oxo-1-((3′-(trifluoromethyl)biphenyl-2-yl)methyl)-1,4-dihydro-1,5-naphthyridine-3-carboxylate (32) (126 mg, 37% yield) as a light brown solid.

Workup

  1. temperatureThen, it was cooled to room temperature
  2. customno solids precipitated
  3. extractionThen, the organic compound was extracted with dichloromethane
  4. washthe combined extracts were washed with water and brine solution
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationFiltration and concentration
  7. customgave the crude brown oil which
  8. customwas purified
  9. washeluting with ethyl acetate in hexanes (0 to 100%)
  10. customthe solvent was removed under vacuum

Sources & evidence

ORD record
ord-48edba8b8e8b46b98f8fc1a8c89441e1
Source dataset
uspto-grants-2015_12
Patent number
US09199987B2

Reaction notes

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