Methanol → 2-[4-(4-acetyl-3,5-dimethyl-piperazin-1-yl)-phenyl]-7-fluoro-5-methoxy-3H-quinazolin-4-one

HRID 591599Notes

Reaction equation

HRID 591599 reaction equation
[C:1]([N:4]1[CH:9]([CH3:10])[CH2:8][N:7]([C:11]2[CH:16]=[CH:15][C:14]([C:17]3[NH:26][C:25](=[O:27])[C:24]4[C:19](=[CH:20][C:21]([F:29])=[CH:22][C:23]=4F)[N:18]=3)=[CH:13][CH:12]=2)[CH2:6][CH:5]1[CH3:30])(=[O:3])[CH3:2].[CH3:31][O-:32].[Na+].CO.O>CN(C=O)C.C(O)(=O)C>[C:1]([N:4]1[CH:5]([CH3:30])[CH2:6][N:7]([C:11]2[CH:12]=[CH:13][C:14]([C:17]3[NH:26][C:25](=[O:27])[C:24]4[C:19](=[CH:20][C:21]([F:29])=[CH:22][C:23]=4[O:32][CH3:31])[N:18]=3)=[CH:15][CH:16]=2)[CH2:8][CH:9]1[CH3:10])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 887MethanolHCID 962WaterHCID 10942334Sodium MethoxideHCID 1363480482-[4-(4-acetyl-3,5-dimethyl-piperazin-1-yl)-phenyl]-5,7-difluoro-3H-quinazolin-4-one

Product 1

HCID 1363480522-[4-(4-acetyl-3,5-dimethyl-piperazin-1-yl)-phenyl]-7-fluoro-5-methoxy-3H-quinazolin-4-one

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-[4-(4-acetyl-3,5-dimethyl-piperazin-1-yl)-phenyl]-5,7-difluoro-3H-quinazolin-4-one (0.66 g, 1.60 mmol) in DMF (10 mL), a solution of sodium methoxide in methanol (25 wt %, 3.5 mL, 16.0 mmol) was added and the reaction mixture was stirred at room temperature for 16 hours. Water was added, acidified to pH approximately 4-5 with acetic acid, and the precipitated solid was filtered and dried under vacuum to give crude compound, which was further purified by column chromatography (silica gel 230-400 mesh; eluting with 2% methanol solution in dichloromethane) to yield 2-[4-(4-acetyl-3,5-dimethyl-piperazin-1-yl)-phenyl]-7-fluoro-5-methoxy-3H-quinazolin-4-one as a light yellow solid.

Workup

  1. filtrationthe precipitated solid was filtered
  2. customdried under vacuum
  3. customto give crude compound, which
  4. customwas further purified by column chromatography (silica gel 230-400 mesh; eluting with 2% methanol solution in dichloromethane)

Sources & evidence

ORD record
ord-c505d11fa977405596ef1880a49fb84f
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

Loading…