Hydrochloric Acid → HCID 23228244, compound

HRID 1596284Notes

Reaction equation

HRID 1596284 reaction equation
Cl.[Cl:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:15][CH2:16][CH2:17][CH2:18][N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)=[C:10]([O:13][CH3:14])[CH:11]=2)[N:6]=[CH:5][N:4]=1.[C:25]([C:27]1[CH:33]=[CH:32][C:30]([NH2:31])=[C:29]([F:34])[CH:28]=1)#[N:26]>C(O)(C)C>[ClH:2].[C:25]([C:27]1[CH:33]=[CH:32][C:30]([NH:31][C:3]2[C:12]3[C:7](=[CH:8][C:9]([O:15][CH2:16][CH2:17][CH2:18][N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)=[C:10]([O:13][CH3:14])[CH:11]=3)[N:6]=[CH:5][N:4]=2)=[C:29]([F:34])[CH:28]=1)#[N:26]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 27564314-Amino-3-fluorobenzonitrileHCID 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline

Product 1

HCID 23228244HCID 23228244, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

5M Isopropanolic hydrogen chloride (1.5 ml) was added to a solution of 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (202 mg, 0.6 mmol), (prepared as described for the starting material in Example 18), and 4-cyano-2-fluoroaniline (100 mg, 0.72 mmol), (U.S. Pat. No. 4,120,693), in isopropanol (5 ml) heated at 50° C. The mixture was then heated at 80° C. for 2 hours, allowed to cool to ambient temperature and left standing overnight. The resulting precipitate was collected by filtration and the solid was then partitioned between methylene chloride and water and 1M aqueous sodium hydroxide solution (0.8 ml) was added. The organic layer was separated, washed with brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by flash chromatography eluting with methylene chloride/methanol (94/6). The purified solid was dissolved in methylene chloride and 2.2M ethereal hydrogen chloride was added. The precipitated product was collected by filtration, washed with ether and dried under vacuum to give 4-(4-cyano-2-fluoroanilino)-6-methoxy 7-(3-morpholinopropoxy)quinazoline hydrochloride (125 mg, 39%).

Workup

  1. custom(prepared
  2. temperatureto cool to ambient temperature
  3. waitleft
  4. filtrationThe resulting precipitate was collected by filtration
  5. customthe solid was then partitioned between methylene chloride and water and 1M aqueous sodium hydroxide solution (0.8 ml)
  6. additionwas added
  7. customThe organic layer was separated
  8. washwashed with brine
  9. dry with materialdried (MgSO4)
  10. customthe solvent removed by evaporation
  11. customThe residue was purified by flash chromatography
  12. washeluting with methylene chloride/methanol (94/6)
  13. dissolutionThe purified solid was dissolved in methylene chloride
  14. addition2.2M ethereal hydrogen chloride was added
  15. filtrationThe precipitated product was collected by filtration
  16. washwashed with ether
  17. customdried under vacuum

Sources & evidence

ORD record
ord-38366807912e460d9e1e3d7d5dda28b8
Source dataset
uspto-grants-2001_09
Patent number
US06291455B1

Reaction notes

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