Cerous carbonate → 2-Chloro-6-(3,5-dimethoxyphenyl)-5-fluoroquinazoline

HRID 56479

Reaction equation

Br[C:2]1[C:3]([F:13])=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([Cl:12])[N:6]=[CH:5]2.[CH3:14][O:15][C:16]1[CH:17]=[C:18](B(O)O)[CH:19]=[C:20]([O:22][CH3:23])[CH:21]=1.C(=O)([O-])[O-].[Ce+3].C(=O)([O-])[O-].C(=O)([O-])[O-].[Ce+3]>C1COCC1.O.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[Cl:12][C:7]1[N:6]=[CH:5][C:4]2[C:9](=[CH:10][CH:11]=[C:2]([C:18]3[CH:17]=[C:16]([O:15][CH3:14])[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=3)[C:3]=2[F:13])[N:8]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 6-bromo-2-chloro-5-fluoroquinazoline (1.5 g, 5.74 mmol), 3,5-dimethoxyphenylboronic acid (1.15 g, 6.31 mmol), cerium carbonate (1.87 g, 5.74 mmol) and bis(tri-tert-butylphosphine)palladium (148 mg, 0.29 mmol) in THF (30 mL) and water (3 mL) was degassed with nitrogen for three times and stirred at 80° C. overnight. The mixture was cooled to room temperature and extracted with ethyl acetate (3×200 mL). The combined organic layers were washed with water and brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (petroleum ether:ethyl acetate=8:1) to get the title product as a white solid (1.3 g, 70%). MS (ES+) C16H12ClFN2O2 requires: 318, found: 319, 321 [M+H]+.

Workup

customwas degassed with nitrogen for three times
temperatureThe mixture was cooled to room temperature
extractionextracted with ethyl acetate (3×200 mL)
washThe combined organic layers were washed with water and brine
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe residue was purified by silica gel chromatography (petroleum ether:ethyl acetate=8:1)

Sources & evidence

ORD record: ord-9c3ceb70829d421fa82865e1e665d467
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09434700B2

Linked notes

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