5-Amino-2-chloro-4-fluorophenol → HCID 22646597, 화합물

HRID 393633노트

반응식

HRID 393633 반응식
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

참가 물질

5

반응물 2

HCID 1586545-Amino-2-chloro-4-fluorophenolHCID 22646629HCID 22646629, 화합물

생성물 1

HCID 22646597HCID 22646597, 화합물수율 54.4%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 223862-Pentanol용매

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-564b68063bc94d72a13c033e183533d0
출처 데이터셋
uspto-grants-2004_10
특허 번호
US06809097B1

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