Dimethylformamide → 4-Oxo-1-((3'-(trifluoromethyl)biphenyl-2-yl)methyl)-1,4-dihydro-1,5-naphthyridine-3-carboxylic acid

HRID 1497692Notes

Reaction equation

HRID 1497692 reaction equation
[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][N:10]=2)[N:5]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=2)[CH:4]=[C:3]1[C:29]([O:31]CC)=[O:30].O.[OH-].[Li+].CN(C)C=O>CO.O.C(#N)C>[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][N:10]=2)[N:5]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=2)[CH:4]=[C:3]1[C:29]([OH:31])=[O:30]

Participants

7

Reactant 3

HCID 6228DimethylformamideHCID 168937Lithium hydroxide, monohydrateHCID 86725446Ethyl 4-oxo-1-((3'-(trifluoromethyl)biphenyl-2-yl)methyl)-1,4-dihydro-1,5-naphthyridine-3-carboxylate

Product 1

HCID 769026744-Oxo-1-((3'-(trifluoromethyl)biphenyl-2-yl)methyl)-1,4-dihydro-1,5-naphthyridine-3-carboxylic acidYield 55.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

To a light brown solution of ethyl 4-oxo-1-((3′-(trifluoromethyl)biphenyl-2-yl)methyl)-1,4-dihydro-1,5-naphthyridine-3-carboxylate (32) (114 mg, 0.252 mmol) in methanol (10 mL) was added the solid lithium hydroxide monohydrate (211 mg, 5.04 mmol) at room temperature under a nitrogen atmosphere. The resulting brown solution was stirred for 15 h at which time LCMS analysis indicated the absence of starting material. Then, the reaction mixture was diluted with water and the methanol was removed under vacuum. The basic aqueous solution contains some solids which were dissolved by addition of 5 mL of dimethylformamide and then it was neutralized with 1.0N HCl. Then, the organic compound was extracted into ethyl acetate (2×50 mL) and the combined extracts were washed with brine solution and dried over anhydrous MgSO4. Filtration and concentration gave the crude oil (may contain some dimethylformamide) which was diluted with acetonitrile and water. Then, it was frozen and lyophilized over 3 days to isolate 4-oxo-1-((3′-(trifluoromethyl)biphenyl-2-yl)methyl)-1,4-dihydro-1,5-naphthyridine-3-carboxylic acid (33) (59 mg, 55% yield) as a light brown solid.

Workup

  1. customthe methanol was removed under vacuum
  2. dissolutionwere dissolved by addition of 5 mL of dimethylformamide
  3. extractionThen, the organic compound was extracted into ethyl acetate (2×50 mL)
  4. washthe combined extracts were washed with brine solution
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationFiltration and concentration
  7. customgave the crude oil (
  8. temperatureThen, it was frozen
  9. waitlyophilized over 3 days

Sources & evidence

ORD record
ord-ea4fffe0249e49ccb244115e40e7caef
Source dataset
uspto-grants-2015_12
Patent number
US09199987B2

Reaction notes

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