Potassium Carbonate → 7-(4-Chlorobutoxy)-N-(4-chloro-2-fluorophenyl)-6-methoxy-4-quinazolinamine

HRID 1596294Notes

Reaction equation

HRID 1596294 reaction equation
[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([OH:19])=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:22])[CH:3]=1.Br[CH2:24][CH2:25][CH2:26][CH2:27][Cl:28].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:28][CH2:27][CH2:26][CH2:25][CH2:24][O:19][C:13]1[CH:12]=[C:11]2[C:16]([C:7]([NH:6][C:5]3[CH:20]=[CH:21][C:2]([Cl:1])=[CH:3][C:4]=3[F:22])=[N:8][CH:9]=[N:10]2)=[CH:15][C:14]=1[O:17][CH3:18]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 813641-Bromo-4-chlorobutaneHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 107402927-(4-Chlorobutoxy)-N-(4-chloro-2-fluorophenyl)-6-methoxy-4-quinazolinamineYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (3.6 g, 11.3 mmol), (prepared as described for the starting material in Example 4), 1 bromo-4-chlorobutane (1.95 ml, 16.9 mmol) and potassium carbonate (4.66 g, 33.8 mmol) in DMF (75 ml) was heated at 40° C. for 4 hours. The mixture was allowed to cool and was partitioned between methylene chloride and water. The aqueous layer was adjusted to pH7 with 2M hydrochloric acid. The organic layer was separated, washed with brine, dried (MgSO4) and the volatiles removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/ethyl acetate (1/1). The purified solid product was triturated with pentane, collected by filtration and dried under vacuum to give 7-(4-chlorobutoxy)-4(4chloro-2-fluoroanilino)-6-methoxyquinazoline (3.64 g, 79%).

Workup

  1. custom(prepared
  2. temperatureto cool
  3. customwas partitioned between methylene chloride and water
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. customthe volatiles removed by evaporation
  8. customThe residue was purified by column chromatography
  9. washeluting with methylene chloride/ethyl acetate (1/1)
  10. customThe purified solid product was triturated with pentane
  11. filtrationcollected by filtration
  12. customdried under vacuum

Sources & evidence

ORD record
ord-015d55482be24e88872f094536fc9758
Source dataset
uspto-grants-2001_09
Patent number
US06291455B1

Reaction notes

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