Dimethylformamide → 4-(2-Fluoro-5-hydroxy-4-methylanilino)-6-methoxy-7-(3-morpholinopropoxy)quinoline hydrochloride hydrate

HRID 393616Notes

Reaction equation

HRID 393616 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][CH:4]=1.[F:25][C:26]1[CH:32]=[C:31]([CH3:33])[C:30]([OH:34])=[CH:29][C:27]=1[NH2:28].CN(C=O)C>CC(O)CCC>[OH2:13].[ClH:2].[F:25][C:26]1[CH:32]=[C:31]([CH3:33])[C:30]([OH:34])=[CH:29][C:27]=1[NH:28][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][CH:4]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 101540985-Amino-4-fluoro-2-methylphenolHCID 226466224-Chloro-6-methoxy-7-(3-morpholinopropoxy)quinoline hydrochloride

Product 1

HCID 226465114-(2-Fluoro-5-hydroxy-4-methylanilino)-6-methoxy-7-(3-morpholinopropoxy)quinoline hydrochloride hydrateYield 228.2%

Reagents, catalysts & solvents 1

HCID 223862-PentanolSolvent

Procedure

A solution of 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinoline hydrochloride (205 mg, 0.5 mmol), (prepared as described for the starting material in Example 7), and 2-fluoro-5-hydroxy-4-methylaniline (70 mg, 0.5 mmol), (prepared as described for the starting material in Example 1), in 2-pentanol (10 ml) and DMF (1 ml) was heated at reflux for 5 hours. The resulting solid was collected by filtration, partitioned between methylene chloride and aqueous sodium hydrogen carbonate solution. The organic layer was separated and purified by column chromatography eluting with methylene chloride/methanol (70/30). The purified solid product was dissolved in ethanol and concentrated hydrochloric acid (0.2 ml) added. The volatiles were removed by evaporation and the residue was recrystallised from isopropanol/ether to give 4-(2-fluoro-5-hydroxy-4-methylanilino)-6-methoxy-7-(3-morpholinopropoxy)quinoline hydrochloride hydrate (283 mg, 73%) as a yellow solid.

Workup

  1. custom(prepared
  2. temperatureat reflux for 5 hours
  3. filtrationThe resulting solid was collected by filtration
  4. custompartitioned between methylene chloride and aqueous sodium hydrogen carbonate solution
  5. customThe organic layer was separated
  6. custompurified by column chromatography
  7. washeluting with methylene chloride/methanol (70/30)
  8. dissolutionThe purified solid product was dissolved in ethanol
  9. additionconcentrated hydrochloric acid (0.2 ml) added
  10. customThe volatiles were removed by evaporation
  11. customthe residue was recrystallised from isopropanol/ether

Sources & evidence

ORD record
ord-9067b591c02c4eccb3fded6540385053
Source dataset
uspto-grants-2004_10
Patent number
US06809097B1

Reaction notes

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