Sodium Hydroxide → 3-Amino-6-chloro-2-(2'-fluoro[1,1'-biphenyl]-4-yl)-4-quinolinecarboxylic acid

HRID 1073264Notes

Reaction equation

HRID 1073264 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=O.[OH-:13].[Na+].Cl.[NH2:16][CH2:17][C:18]([C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[F:32])=[CH:22][CH:21]=1)=O>O.C(O)C.O1CCCC1>[NH2:16][C:17]1[C:18]([C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[F:32])=[CH:22][CH:21]=2)=[N:7][C:8]2[C:4]([C:5]=1[C:6]([OH:11])=[O:13])=[CH:3][C:2]([Cl:1])=[CH:10][CH:9]=2

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 872035-chloro-1H-indole-2,3-dioneHCID 221583512-Amino-1-(2'-fluoro[1,1'-biphenyl]-4-yl)-ethanone hydrochloride

Product 1

HCID 150859613-Amino-6-chloro-2-(2'-fluoro[1,1'-biphenyl]-4-yl)-4-quinolinecarboxylic acidYield 67.2%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolvent3×HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred suspension of 4.54 g of 5-chloroisatin in 40 ml of water was added a solution of 5.62 g of sodium hydroxide in 20 ml of water. To the resulting solution at 85°-90° C. was added dropwise over 2 hours, a warm solution of 9.3 g of 2-amino-1-(2'-fluoro[1,1'-biphenyl]-4-yl)ethanone, hydrochloride in 70 ml of water, 70 ml of ethanol and 30 ml of tetrahydrofuran. This mixture was stirred at reflux for 2 hours then the ethanol was distilled off. The reaction was cooled in an ice bath, the solid collected and washed with water. This solid was stirred in 800 ml of water for 2 hours and then filtered. The filtrate was acidified to pH 4-5 with acetic acid. The resulting solid was collected, washed with water and dried, giving 6.6 g of the desired product as a yellow solid, mp 247°-249° C.

Workup

  1. additionTo the resulting solution at 85°-90° C. was added dropwise over 2 hours
  2. temperatureat reflux for 2 hours
  3. distillationthe ethanol was distilled off
  4. temperatureThe reaction was cooled in an ice bath
  5. customthe solid collected
  6. washwashed with water
  7. stirringThis solid was stirred in 800 ml of water for 2 hours
  8. filtrationfiltered
  9. customThe resulting solid was collected
  10. washwashed with water
  11. customdried

Sources & evidence

ORD record
ord-c466d1a913174c4aa50f657a10a38e0e
Source dataset
uspto-grants-1990_11
Patent number
US04968702

Reaction notes

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