Water → 6-fluoro-3-(4-methoxy-benzyl)-1-phenyl-3,4-dihydro-1H-pyrido[3,2-d]pyrimidin-2-one

HRID 1749093Notes

Reaction equation

HRID 1749093 reaction equation
Br[C:2]1[C:3]([CH2:9][N:10]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)[C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:12])=[N:4][C:5]([F:8])=[CH:6][CH:7]=1.C(N(CC)C(C)C)(C)C.O>CN(C=O)C.[Cu]I>[F:8][C:5]1[CH:6]=[CH:7][C:2]2[N:13]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:11](=[O:12])[N:10]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=3)[CH2:9][C:3]=2[N:4]=1

Participants

6

Reactant 3

HCID 962WaterHCID 81531DiisopropylethylamineHCID 70981131(3-Bromo-6-fluoro-pyridin-2-ylmethyl)-(4-methoxy-benzyl)-3-phenyl-urea

Product 1

HCID 709803326-fluoro-3-(4-methoxy-benzyl)-1-phenyl-3,4-dihydro-1H-pyrido[3,2-d]pyrimidin-2-oneYield 55%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of (3-bromo-6-fluoro-pyridin-2-ylmethyl)-(4-methoxy-benzyl)-3-phenyl-urea (644 mg, 1.5 mmol, 1.0 equiv) and N,N-diisopropylethylamine (500 μL, 2.9 mmol, 2.0 equiv) in DMF (15 mL) was added CuI (331 mg, 1.7 mmol, 1.2 equiv) and the reaction mixture was heated at 150° C. for 5 h. The reaction mixture was cooled, H2O was added and the product was extracted with EtOAc. The organic phase was washed with dilute NH4OH, brine, dried (MgSO4), filtered and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO2, eluted with petrol—EtOAc 0-50%) to afford 6-fluoro-3-(4-methoxy-benzyl)-1-phenyl-3,4-dihydro-1H-pyrido[3,2-d]pyrimidin-2-one (300 mg). MS: [M+H]+=364.

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionthe product was extracted with EtOAc
  3. washThe organic phase was washed with dilute NH4OH, brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by column chromatography (SiO2, eluted with petrol—EtOAc 0-50%)

Sources & evidence

ORD record
ord-ee784f195a994816a271931cca2cd439
Source dataset
uspto-grants-2015_10
Patent number
US09155743B2

Reaction notes

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