Dichloromethane → 4-Chloro-6-fluoro-2-(3,4,5-trimethoxyphenyl)quinazoline

HRID 717358Notes

Reaction equation

HRID 717358 reaction equation
[F: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])[C:15]([O:20][CH3:21])=[C:14]([O:22][CH3:23])[CH:13]=1)[N:6]=[C:5]2O.[Cl:25]CCl.C(Cl)(C(Cl)=O)=O>CN(C)C=O>[Cl:25][C:5]1[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([F:1])[CH:3]=2)[N:8]=[C:7]([C:12]2[CH:17]=[C:16]([O:18][CH3:19])[C:15]([O:20][CH3:21])=[C:14]([O:22][CH3:23])[CH:13]=2)[N:6]=1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 65578Oxalyl chlorideHCID 1784880196-fluoro-2-(3,4,5-trimethoxyphenyl)-1H-quinazolin-4-one

Product 1

HCID 904103884-Chloro-6-fluoro-2-(3,4,5-trimethoxyphenyl)quinazoline

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Into a 500-mL round-bottom flask, was placed 6-fluoro-2-(3,4,5-trimethoxyphenyl)quinazolin-4-ol (8.0 g, 24.22 mmol, 1.00 equiv), dichloromethane (200 mL) and N,N-dimethylformamide (0.5 mL). This was followed by the addition of (COCl)2 (23.74 g) dropwise with stirring. The resulting solution was stirred for 1 h at 40° C. in an oil bath. The resulting mixture was concentrated under vacuum. The residue was dissolved in 100 mL of dichloromethane. The resulting mixture was washed with 2×100 mL of NaHCO3 (sat.) and 1×100 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by ethyl acetate:petroleum ether in ratio of (1:5). This resulted in 5 g (59%) of 4-chloro-6-fluoro-2-(3,4,5-trimethoxyphenyl)quinazoline as a white solid. MS (ESI) m/z 349 ([M+H]+).

Workup

  1. customInto a 500-mL round-bottom flask, was placed
  2. stirringThe resulting solution was stirred for 1 h at 40° C. in an oil bath
  3. concentrationThe resulting mixture was concentrated under vacuum
  4. dissolutionThe residue was dissolved in 100 mL of dichloromethane
  5. washThe resulting mixture was washed with 2×100 mL of NaHCO3 (sat.) and 1×100 mL of brine
  6. dry with materialThe mixture was dried over anhydrous sodium sulfate
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by ethyl acetate
  9. customThis resulted in 5 g (59%) of 4-chloro-6-fluoro-2-(3,4,5-trimethoxyphenyl)quinazoline as a white solid

Sources & evidence

ORD record
ord-2b8499708d6c43159bc7d699062711ee
Source dataset
uspto-grants-2015_11
Patent number
US09193707B2

Reaction notes

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