Cesium carbonate → 2-Chloro-6-(3,5-dimethoxyphenyl)-8-fluoroquinazoline

HRID 2274225Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([F:12])[CH:11]=1)[N:8]=[C:7]([Cl:13])[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-].[Cs+].[Cs+]>C1COCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:13][C:7]1[N:6]=[CH:5][C:4]2[C:9](=[C:10]([F:12])[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)[CH:3]=2)[N:8]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 6-bromo-2-chloro-8-fluoroquinazoline (4.0 g, 15.4 mmol), 3,5-dimethoxyphenylboronic acid (4.47 g, 16.9 mmol), cesium carbonate (10.0 g, 30.8 mmol) and Pd(PPh3)2Cl2 (236 mg, 0.77 mmol) in THF (200 mL) and water (10 mL) was degassed with nitrogen three times, and stirred at 80° C. for 3 h. Both TLC and LCMS showed the reaction was completed. The reaction mixture was cooled to RT and directly concentrated. The residue was purified by silica gel chromatography (petroleum ether:dichloromethane=2:1 to 1:1) to afford the title compound (2.5 g, 51%) as a yellow solid. MS (ES+) C16H12ClFN2O2 requires: 318/320. Found: 319/321 [M+H]+.

Workup

customwas degassed with nitrogen three times
temperatureThe reaction mixture was cooled to RT
concentrationdirectly concentrated
customThe residue was purified by silica gel chromatography (petroleum ether:dichloromethane=2:1 to 1:1)

Sources & evidence

ORD record: ord-25d497a076af492cb977ce5c0a777a13
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09126951B2

Reaction notes

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