Acetic Acid → 6-(4-Fluorophenyl)pyrido[3,2-d]pyrimidin-4(1H)-one

HRID 1517437Notes

Reaction equation

HRID 1517437 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]=[CH:7][NH:8][C:9](=[O:12])[C:10]=2[N:11]=1.[F:13][C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][CH:15]=1.C([O-])([O-])=O.[K+].[K+].C(O)(=O)C>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:13][C:14]1[CH:19]=[CH:18][C:17]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]=[CH:7][NH:8][C:9](=[O:12])[C:10]=3[N:11]=2)=[CH:16][CH:15]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 11430Potassium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 1354270966-Chloropyrido[3,2-d]pyrimidin-4(3H)-one

Product 1

HCID 1360008906-(4-Fluorophenyl)pyrido[3,2-d]pyrimidin-4(1H)-oneYield 90.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 6-chloro-pyrido[3,2-d]pyrimidin-4(3H)one (1.0 g, 5.5 mmol) in dioxane (80 ml) and water (20 ml) was added 4-fluorophenylboronic acid (770 mg, 5.5 mmol), K2CO3 (2.28 g, 16.5 mmol), and tetrakis(triphenylphosphine)palladium(0) (290 mg, 0.25 mmol). The mixture was heated at reflux for 20 hours. After cooling to room temperature, the reaction mixture was neutralized to pH 5-6 with acetic acid, concentrated to a small volume, filtered and washed with water to yield a crude product. The crude residue was purified by silica gel flash chromatography, the mobile phase being a mixture of methanol and dichloromethane, in a volume ratio of 1:30, yielding the title compound as a white solid (1.2 g, yield: 90%) which was characterised by its mass spectrum as follows: MS (m/z): 242 ([M+H]+, 100).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 20 hours
  3. concentrationconcentrated to a small volume
  4. filtrationfiltered
  5. washwashed with water
  6. customto yield a crude product
  7. customThe crude residue was purified by silica gel flash chromatography
  8. additiona mixture of methanol and dichloromethane

Sources & evidence

ORD record
ord-4b5a421e92324505a837009abfae4496
Source dataset
uspto-grants-2012_07
Patent number
US08232278B2

Reaction notes

Loading…