Potassium Carbonate → HCID 53869717, compound

HRID 1737636Notes

Reaction equation

HRID 1737636 reaction equation
[OH:1][CH:2]=[CH:3][CH2:4][C:5]1[CH:10]=[CH:9][N:8]=[CH:7][CH:6]=1.S(Cl)(Cl)=O.[Cl:15][C:16]1[CH:35]=[CH:34][C:19]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27](O)=[C:28]([O:31][CH3:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)=[C:18]([F:36])[CH:17]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.CN(C=O)C>[Cl:15][C:16]1[CH:35]=[CH:34][C:19]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:1][CH2:2][CH:3]=[CH:4][C:5]4[CH:10]=[CH:9][N:8]=[CH:7][CH:6]=4)=[C:28]([O:31][CH3:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)=[C:18]([F:36])[CH:17]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 67726470HCID 67726470, compoundHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 53869717HCID 53869717, compoundYield 4%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-(3-hydroxyprop-2-en-1-yl)pyridine (180 mg, 1.3 mmol) and thionyl chloride (0.3 ml) in toluene (10 ml) was stirred at room temperature for 2 hours. The volatiles were removed by evaporation to give crude 4-(3-chloroprop-2-en-1-yl)pyridine hydrochloride (180 mg, 0.94 mmol)) This product was added to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (500 mg, 1.6 mmol) and potassium carbonate (500 mg, 4.9 mmol) in DMF (20 ml) and the mixture stirred at 100° C. for 1 hour. The reaction mixture was allowed to cool and partitioned between ethyl acetate and water. The organic layer was separated, washed with water and brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (100/0 increasing to 95/5) and then by reverse phase (C18) HPLC eluting with methanol/water (30/70 increasing to 50/50) to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(3-(pyrid-4-yl)prop-2-en-1-yloxy)quinazoline (15 mg, 4%).

Workup

  1. customThe volatiles were removed by evaporation
  2. customto give crude 4-(3-chloroprop-2-en-1-yl)pyridine hydrochloride (180 mg, 0.94 mmol)) This product
  3. stirringthe mixture stirred at 100° C. for 1 hour
  4. temperatureto cool
  5. custompartitioned between ethyl acetate and water
  6. customThe organic layer was separated
  7. washwashed with water and brine
  8. dry with materialdried (MgSO4)
  9. customthe solvent removed by evaporation
  10. customThe residue was purified by column chromatography
  11. washeluting with methylene chloride/methanol (100/0 increasing to 95/5)
  12. washby reverse phase (C18) HPLC eluting with methanol/water (30/70 increasing to 50/50)

Sources & evidence

ORD record
ord-56717b9319ce468fb1a4210a9c7b33f2
Source dataset
uspto-grants-1999_10
Patent number
US05962458

Reaction notes

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