Sodium Acetate → N-[4-(Difluoromethoxy)phenyl]-2-methylquinazolin-4-amine

HRID 1876109Notes

Reaction equation

HRID 1876109 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([CH3:12])[N:3]=1.[F:13][CH:14]([F:23])[O:15][C:16]1[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=1.C([O-])(=O)C.[Na+]>C(OCC)(=O)C>[F:13][CH:14]([F:23])[O:15][C:16]1[CH:17]=[CH:18][C:19]([NH:22][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=[C:4]([CH3:12])[N:3]=2)=[CH:20][CH:21]=1

Participants

5

Reactant 3

HCID 517045Sodium AcetateHCID 7373634-(Difluoromethoxy)anilineHCID 27854214-Chloro-2-methylquinazoline

Product 1

HCID 42625916N-[4-(Difluoromethoxy)phenyl]-2-methylquinazolin-4-amineYield 94%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 4-chloro-2-methyl-quinazoline (450 mg, 2.52 mmol), 4-difluoromethoxy-phenylamine (0.32 ml, 2.52 mmol) and sodium acetate (248.07 mg, 3.02 mmol) in 6 mL of solvent (THF:water=1:1) was stirred at 70° C. for 1 h. The reaction mixture was diluted with 30 mL of ethyl acetate. It was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated. The crude product was purified by chromatography on silica gel with acetate and hexane (1:5) as eluent, yielding 713 mg of title compound (94%). 1H NMR (CDCl3): 7.87-7.76 (m, 5H), 7.51 (t, J=8.4 Hz, 1H)), 7.40 (brs, 1H), 7.19 (d, J=8.7 Hz, 2H), 6.76-6.27 (three single peaks, 1H), 2.71 (s, 3H).

Workup

  1. washIt was washed with brine
  2. dry with materialdried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was purified by chromatography on silica gel with acetate and hexane (1:5) as eluent

Sources & evidence

ORD record
ord-c9c07efe42974b8c988d77b1f4e0aa8c
Source dataset
uspto-grants-2012_11
Patent number
US08309562B2

Reaction notes

Loading…