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

HRID 393633Notes

Reaction equation

HRID 393633 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[CH2:23][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

Participants

5

Reactant 2

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

Product 1

HCID 22646597HCID 22646597, compoundYield 54.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 223862-PentanolSolvent

Procedure

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%).

Workup

  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

Sources & evidence

ORD record
ord-564b68063bc94d72a13c033e183533d0
Source dataset
uspto-grants-2004_10
Patent number
US06809097B1

Reaction notes

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