Cesium carbonate → 7-Methoxy-6-(2-methylphenyl)-N-phenylquinazolin-2-amine

HRID 602387Notes

Reaction equation

HRID 602387 reaction equation
[NH2:1][C:2]1[N:11]=[CH:10][C:9]2[C:4](=[CH:5][C:6]([O:19][CH3:20])=[C:7]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[CH3:18])[CH:8]=2)[N:3]=1.I[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[NH:1]([C:2]1[N:11]=[CH:10][C:9]2[C:4](=[CH:5][C:6]([O:19][CH3:20])=[C:7]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[CH3:18])[CH:8]=2)[N:3]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 11575IodobenzeneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 670614707-Methoxy-6-(2-methylphenyl)quinazolin-2-amine

Product 1

HCID 670616607-Methoxy-6-(2-methylphenyl)-N-phenylquinazolin-2-amineYield 85%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

2-Amino-7-methoxy-6-(2-methylphenyl)quinazoline (150 mg, 0.565 mmol) obtained in Example 174 was dissolved in dioxane (5.7 mL) and the solution was added with iodobenzene (70 μL, 0.622 mmol), tris(dibenzylideneacetone)dipalladium (25.9 mg, 0.028 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (36 mg, 0.062 mmol) and cesium carbonate (258 mg, 0.791 mmol), followed by stirring at 100° C. for 20 hours. The reaction mixture was added with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, then the solvent was evaporated under reduced pressure. The residue was purified by preparative thin-layer chromatography (ethyl acetate/hexane=3/7) to obtain 2-anilino-7-methoxy-6-(2-methylphenyl)quinazoline (164 mg, 85%). In a similar manner to Example 19, Compound 178 was obtained using the above-obtained 2-anilino-7-methoxy-6-(2-methylphenyl)quinazoline.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by preparative thin-layer chromatography (ethyl acetate/hexane=3/7)

Sources & evidence

ORD record
ord-dc3b55c38ec544ff8cd657fe4c490e77
Source dataset
uspto-grants-2011_03
Patent number
US07906522B2

Reaction notes

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