Morpholine → HCID 21701588, compound

HRID 1596293Notes

Reaction equation

HRID 1596293 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([C:11]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=3[F:25])=[N:12][CH:13]=[N:14]2)=[CH:9][C:8]=1[O:26][CH3:27].[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1>>[ClH:1].[Cl:24][C:21]1[CH:22]=[CH:23][C:18]([NH:17][C:11]2[C:10]3[C:15](=[CH:16][C:7]([O:6][CH2:5][CH2:4][CH2:3][CH2:2][N:28]4[CH2:33][CH2:32][O:31][CH2:30][CH2:29]4)=[C:8]([O:26][CH3:27])[CH:9]=3)[N:14]=[CH:13][N:12]=2)=[C:19]([F:25])[CH:20]=1

Participants

3

Reactant 2

HCID 8083MorpholineHCID 107402927-(4-Chlorobutoxy)-N-(4-chloro-2-fluorophenyl)-6-methoxy-4-quinazolinamine

Product 1

HCID 21701588HCID 21701588, compoundYield 78%

Procedure

A solution of 7-(4-chlorobutoxy)4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline (3.64 g, 8.87 mmol) in morpholine (70 ml) was heated at 110° C. for 2 hours. The mixture was allowed to cool and was partitioned between ethyl acetate and water. 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 and methanol (92/8). The purified solid product was dissolved in methylene chloride and 3M ethereal hydrogen chloride was added. The volatiles were removed by evaporation, and the residue triturated with ether. The solid was collected by filtration, washed with ether and dried under vacuum at 60° C. to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(4-morpholinobutoxy)quinazoline hydrochloride (3.8 g, 78%).

Workup

  1. temperatureto cool
  2. customwas partitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. customthe volatiles removed by evaporation
  7. customThe residue was purified by column chromatography
  8. washeluting with methylene chloride and methanol (92/8)
  9. dissolutionThe purified solid product was dissolved in methylene chloride
  10. addition3M ethereal hydrogen chloride was added
  11. customThe volatiles were removed by evaporation
  12. customthe residue triturated with ether
  13. filtrationThe solid was collected by filtration
  14. washwashed with ether
  15. customdried under vacuum at 60° C.

Sources & evidence

ORD record
ord-55c186a6c56a4c198d22285c9139e34e
Source dataset
uspto-grants-2001_09
Patent number
US06291455B1

Reaction notes

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