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

HRID 1436271Notes

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

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

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

Sources & evidence

ORD record: ord-63f06db27c104d0485801da52a8e7274
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07618975B2

Reaction notes

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