4-Bromopyridinium chloride → 2-(3,5-Dimethoxyphenyl)-6-(pyridin-4-ylamino)quinazolin-4(3H)-one

HRID 591864Notes

Reaction equation

HRID 591864 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[C:14]([O:20][CH3:21])[CH:13]=1)[NH:6][C:5]2=[O:22].Cl.Br[C:25]1[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=1.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].N1C=CC=CC=1>[CH3:21][O:20][C:14]1[CH:13]=[C:12]([C:7]2[NH:6][C:5](=[O:22])[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([NH:1][C:25]4[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=4)[CH:3]=3)[N:8]=2)[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=1

Participants

7

Reactant 3

HCID 881004-Bromopyridinium chlorideHCID 23676156Sodium t-butoxideHCID 1363480626-amino-2-(3,5-dimethoxy-phenyl)-3H-quinazolin-4-one

Product 1

HCID 1359390832-(3,5-Dimethoxyphenyl)-6-(pyridin-4-ylamino)quinazolin-4(3H)-one

Reagents, catalysts & solvents 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1049PyridineSolvent

Procedure

6-Amino-2-(3,5-dimethoxy-phenyl)-3H-quinazolin-4-one (297 mg, 1.00 mmol), 4-bromopyridine hydrochloride (194 mg, 1.00 mmol), tris(dibenzylideneacetone)dipalladium(0) (18 mg, 0.02 mmol), 1,1′-bis(diphenylphosphino)ferrocene (17 mg, 0.03 mmol), sodium tert-butoxide (230 mg, 2.40 mmol) and pyridine (3 mL) were heated at 140° C. in microwave oven (150 W) for 1 hour. The mixture was concentrated under vacuum to dryness. The residue was purified by column chromatography (silica gel 230-400 mesh; 5% methanol in dichloromethane and then 10% 2 N NH3 in methanol and dichloromethane as eluent) to give the title compound as a brown/beige solid. Yield: 176 mg (47%). MP 289-290° C. 1H NMR (400 MHz, DMSO-d6): δ 9.24 (s, 1H), 8.29 (d, J=5.6 Hz, 2H), 7.90 (s, 1H), 7.75 (d, J=8.8 Hz, 1H), 7.65 (d, J=8.4 Hz, 1H), 7.38 (s, 2H), 7.03 (d, J=5.2 Hz, 2H), 6.69 (s, 1H), 3.85 (s, 6H). MS (ES+) m/z: 375.13 (M+1).

Workup

  1. concentrationThe mixture was concentrated under vacuum to dryness
  2. customThe residue was purified by column chromatography (silica gel 230-400 mesh

Sources & evidence

ORD record
ord-9417de12208c452280d67537ae37a7f0
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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