5-Amino-2-chloro-4-fluorophenol → HCID 22646597、化合物

HRID 393633ノート

反応式

HRID 393633 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[CH2:23][CH2:22][CH2:21][CH2:20]3)=[C:10]([O:13][CH3:14])[CH:11]=2)[N:6]=[CH:5][CH:4]=1.[Cl:24][C:25]1[C:31]([OH:32])=[CH:30][C:28]([NH2:29])=[C:27]([F:33])[CH:26]=1>CC(O)CCC.CN(C=O)C>[ClH:2].[Cl:24][C:25]1[C:31]([OH:32])=[CH:30][C:28]([NH:29][C:3]2[C:12]3[C:7](=[CH:8][C:9]([O:15][CH2:16][CH2:17][CH2:18][N:19]4[CH2:23][CH2:22][CH2:21][CH2:20]4)=[C:10]([O:13][CH3:14])[CH:11]=3)[N:6]=[CH:5][CH:4]=2)=[C:27]([F:33])[CH:26]=1

参加物

5

反応物 2

HCID 1586545-Amino-2-chloro-4-fluorophenolHCID 22646629HCID 22646629、化合物

生成物 1

HCID 22646597HCID 22646597、化合物収率 54.4%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 223862-Pentanol溶媒

実験手順

A solution of 4-chloro-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinoline hydrochloride (325 mg, 0.82 mmol) and 4-chloro-2-fluoro-5-hydroxyaniline (133 mg, 0.82 mmol), (as described in EP 61741 A2), in 2-pentanol (10 ml) and DMF (1 ml) was heated at reflux for 5 hours. The volatiles were removed by evaporation and the residue was purified by column chromatography eluting with acetonitrile/water containing 1% TFA (30/70). Concentrated hydrochloric acid was added to the fractions and the solvents were removed by evaporation. The residue was azeotroped with toluene, and triturated with isopropanol. The solid was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoro-5-hydroxyanilino)-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinoline hydrochloride (215 mg, 50%).

後処理

  1. temperatureat reflux for 5 hours
  2. customThe volatiles were removed by evaporation
  3. customthe residue was purified by column chromatography
  4. washeluting with acetonitrile/water containing 1% TFA (30/70)
  5. additionConcentrated hydrochloric acid was added to the fractions
  6. customthe solvents were removed by evaporation
  7. customThe residue was azeotroped with toluene
  8. customtriturated with isopropanol
  9. filtrationThe solid was collected by filtration
  10. washwashed with ether
  11. customdried under vacuum

出典と根拠

ORDレコード
ord-564b68063bc94d72a13c033e183533d0
出典データセット
uspto-grants-2004_10
特許番号
US06809097B1

反応ノート

読み込み中…