Cerous carbonate → 2-Chloro-6-(3,5-dimethoxyphenyl)-7-methoxyquinazoline

HRID 2274219Notes

Reaction equation

HRID 2274219 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[N:8]=[C:7]([Cl:14])[N:6]=[CH:5]2.[CH3:15][O:16][C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[C:21]([O:23][CH3:24])[CH:22]=1.C(=O)([O-])[O-].[Ce+3].C(=O)([O-])[O-].C(=O)([O-])[O-].[Ce+3]>C1COCC1.O1CCOCC1.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:14][C:7]1[N:6]=[CH:5][C:4]2[C:9](=[CH:10][C:11]([O:12][CH3:13])=[C:2]([C:19]3[CH:18]=[C:17]([O:16][CH3:15])[CH:22]=[C:21]([O:23][CH3:24])[CH:20]=3)[CH:3]=2)[N:8]=1

Participants

8

Reactant 3

HCID 160516Cerous carbonateHCID 4374257(3,5-Dimethoxyphenyl)boronic acidHCID 591992766-Bromo-2-chloro-7-methoxyquinazoline

Product 1

HCID 867135952-Chloro-6-(3,5-dimethoxyphenyl)-7-methoxyquinazolineYield 38%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 6-bromo-2-chloro-7-methoxyquinazoline (2.4 g, 8.82 mmol), 3,5-dimethoxyphenylboronic acid (1.6 g, 8.82 mmol), cerium carbonate (8.6 g, 26.46 mmol) and Pd(PPh3)2Cl2 (1.4 g, 2.1 mmol) in THF (10 mL), dioxane (10 mL) and water (2 mL) was degassed with nitrogen three times and stirred at 85° C. for 3 h. LCMS monitored the reaction was completed. The mixture was cooled to RT and extracted with dichloromethane (3×50 mL). The organic layers were separated, combined, washed with water and brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (petroleum ether:ethyl acetate=1:4) to give the title compound (1.1 g, 38%) as a white solid. MS (ES+) C17H15ClN2O3 requires: 330, 332. Found: 331, 333 [M+H]+.

Workup

  1. customwas degassed with nitrogen three times
  2. temperatureThe mixture was cooled to RT
  3. extractionextracted with dichloromethane (3×50 mL)
  4. customThe organic layers were separated
  5. washwashed with water and brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography (petroleum ether:ethyl acetate=1:4)

Sources & evidence

ORD record
ord-97b38dcdff9344a1a223271e3e9601a8
Source dataset
uspto-grants-2015_09
Patent number
US09126951B2

Reaction notes

Loading…