Potassium Carbonate → HCID 21186979, compound

HRID 1737581Notes

Reaction equation

HRID 1737581 reaction equation
S(Cl)(Cl)=O.[OH:5][CH2:6][CH2:7][CH2:8][S:9][C:10]1[N:11]([CH3:15])[CH:12]=[CH:13][N:14]=1.[Cl:16][C:17]1[CH:36]=[CH:35][C:20]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](O)=[C:29]([O:32][CH3:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)=[C:19]([F:37])[CH:18]=1.C(=O)([O-])[O-].[K+].[K+]>ClC(Cl)Cl.CN1C(=O)CCC1.O>[Cl:16][C:17]1[CH:36]=[CH:35][C:20]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:5][CH2:6][CH2:7][CH2:8][S:9][C:10]4[N:11]([CH3:15])[CH:12]=[CH:13][N:14]=4)=[C:29]([O:32][CH3:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)=[C:19]([F:37])[CH:18]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 22624964HCID 22624964, compoundHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 21186979HCID 21186979, compoundYield 6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6212ChloroformSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
5 °C

Procedure

Thionyl chloride (0.80 ml, 11 mmol) was added to a solution of 2-(3-hydroxypropylthio)-1-methylimidazole (1.25 g, 7.3 mmol) in trichloromethane (25 ml) at 5° C. The mixture was stirred at 5° C. for 1 hour and then at ambient temperature for 2 hours. The volatiles were removed by evaporation, the residue azeotroped with toluene and dried under vacuum to give crude 2-(3-chloropropylthio)-1-methylimidazole hydrochloride (1.0 g) which was used directly. Part of this product (226 mg, 1.0 mmol) was added to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (350 mg, 10 mmol), (prepared as described for the starting material in Example 24), and potassium carbonate (303 mg 2.2 mmol) in NMP (20 ml) and the mixture was heated at 90° C. for 2 hours. The mixture was allowed to cool, diluted with water and extracted with ethyl acetate. The combined extracts were wahed with water, 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) to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(3-(1-methylimidazol-2- ylthio)propoxy)quinazoline (29 mg, 6%).

Workup

  1. waitat ambient temperature for 2 hours
  2. customThe volatiles were removed by evaporation
  3. customthe residue azeotroped with toluene
  4. customdried under vacuum
  5. customto give crude 2-(3-chloropropylthio)-1-methylimidazole hydrochloride (1.0 g) which
  6. custom(prepared
  7. temperaturethe mixture was heated at 90° C. for 2 hours
  8. temperatureto cool
  9. extractionextracted with ethyl acetate
  10. dry with materialdried (MgSO4)
  11. customthe solvent removed by evaporation
  12. customThe residue was purified by column chromatography
  13. washeluting with methylene chloride/methanol (100/0 increasing to 95/5)

Sources & evidence

ORD record
ord-d52d5335182744898f53d49ff4a87355
Source dataset
uspto-grants-1999_10
Patent number
US05962458

Reaction notes

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