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

HRID 2404019Notes

Reaction equation

HRID 2404019 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([Cl:12])[N:6]=[CH:5]2.[CH3:13][O:14][C:15]1[CH:16]=[C:17](B(O)O)[CH:18]=[C:19]([O:21][CH3:22])[CH:20]=1.C([O-])([O-])=O.[Cs+].[Cs+]>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:12][C:7]1[N:6]=[CH:5][C:4]2[C:9](=[CH:10][CH:11]=[C:2]([C:17]3[CH:16]=[C:15]([O:14][CH3:13])[CH:20]=[C:19]([O:21][CH3:22])[CH:18]=3)[CH:3]=2)[N:8]=1

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 4374257(3,5-Dimethoxyphenyl)boronic acidHCID 179135596-Bromo-2-chloroquinazoline

Product 1

HCID 867135642-Chloro-6-(3,5-dimethoxyphenyl)quinazolineYield 38.9%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
80 °C

Procedure

A mixture of 6-bromo-2-chloroquinazoline (32) (5.0 g, 20.5 mmol), 3,5-dimethoxyphenylboronic acid (33) (3.7 g, 20.5 mmol), Cs2CO3 (20.0 g, 61.5 mmol) and Pd(PPh3)2Cl2 (1.4 g, 2.1 mmol) in THF (50 mL), dioxane (50 mL) and water (10 mL) was degassed with N2 three times, and stirred at 80° C. for 3 hours. An aliquot of the reaction mixture was analyzed by both TLC and LCMS, which indicated that the reaction had proceeded to completion. The mixture was cooled to room temperature, and extracted with EtOAc (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/EtOAc=8:1) to obtain 2-chloro-6-(3,5-dimethoxyphenyl)quinazoline (34) as a light yellow solid (2.4 g, 38%). MS (ES+) C16H13ClN2O2 requires: 300. found: 301, 303 [M+H]+.

Workup

  1. customwas degassed with N2 three times
  2. temperatureThe mixture was cooled to room temperature
  3. extractionextracted with EtOAc (3×200 mL)
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography (petroleum ether/EtOAc=8:1)

Sources & evidence

ORD record
ord-ba964729cbf149d08e1687f60355c0a9
Source dataset
uspto-grants-2014_08
Patent number
US08802697B2

Reaction notes

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