Ethanol → HCID 21948209, compound

HRID 1839418Notes

Reaction equation

HRID 1839418 reaction equation
[NH:1]([C:8]1[N:9]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:10]2[C:15]([C:16](=[O:18])[CH:17]=1)=[C:14](Cl)[N:13]=[C:12]([CH3:20])[CH:11]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:27]([O-:30])([O-])=[O:28].[Cs+].[Cs+].[CH3:33][CH2:34]O>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH:1]([C:8]1[N:9]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:10]2[CH:11]=[C:12]([CH3:20])[N:13]=[C:14]([C:27]([O:30][CH2:33][CH3:34])=[O:28])[C:15]=2[C:16](=[O:18])[CH:17]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 702EthanolHCID 10796Cesium carbonateHCID 10269984HCID 10269984, compound

Product 1

HCID 21948209HCID 21948209, compoundYield 71%

Reagents, catalysts & solvents 3

HCID 812191,3-Bis(diphenylphosphino)propaneCatalystHCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

2-Anilino-5-chloro-7-methyl-1-phenyl-1,6-naphthyridin-4(1H)-one (1.0 g, 2.8 mmol), DPPP (64 mg, 0.15 mmol), Pd(OAc)2 (31 mg, 0.14 mmol), Cs2CO3 (580 mg, 4.20 mmol) were dissolved in EtOH (10 mL) and DMF (10 mL). A balloon filled with CO was attached to the flask and the solution was stirred vigorously. The flask was purged with CO for 5 min before it was heated to 70° C. After 4 h the mixture was cooled to room temperature and diluted with EtOAc. The mixture was washed with water, brine, and dried over Na2SO4. Solvents were removed in vacuo and the residue was triturated with Et2O to give ethyl 2-anilino-7-methyl-4-oxo-1-phenyl-1,4-dihydro-1,6-naphthyridine-5-carboxylate (800 mg, 71%). The ethyl ester was then dissolved in MeOH (5 mL), and THF (20 mL). To this stirring solution was added KOH (3N, 10 mL) and the mixture was stirred at room temperature for 6 h before it was extracted with Et2O. The aqueous layer was acidified with 2N HCl to pH=1 and the product precipitated out of the solution. The solid was filtered and dried to give 2-anilino-7-methyl-4-oxo-1-phenyl-1,4-dihydro-1,6-naphthyridine-5-carboxylic acid as a white solid (683 mg, 92%): LCMS RT: 1.75 min, MH+: 372.9.

Workup

  1. additionA balloon filled with CO
  2. customThe flask was purged with CO for 5 min before it
  3. temperatureAfter 4 h the mixture was cooled to room temperature
  4. additiondiluted with EtOAc
  5. washThe mixture was washed with water, brine
  6. dry with materialdried over Na2SO4
  7. customSolvents were removed in vacuo
  8. customthe residue was triturated with Et2O

Sources & evidence

ORD record
ord-eaf789ddddb94fe0898175570e195f3d
Source dataset
uspto-grants-2004_01
Patent number
US06677352B1

Reaction notes

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