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

HRID 393616ノート

反応式

HRID 393616 の反応式
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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 223862-Pentanol溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-9067b591c02c4eccb3fded6540385053
出典データセット
uspto-grants-2004_10
特許番号
US06809097B1

反応ノート

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