4-Chloro-2-fluoroaniline → 4-(4-Chloro-2-fluoro-phenylamino)-7-(3-chloro-propoxy)-6-methoxy-quinoline-3-carbonitrile

HRID 1934951Notes

Reaction equation

HRID 1934951 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10](Cl)=[C:11]([C:16]#[N:17])[CH:12]=[N:13]2)=[CH:8][C:7]=1[O:19][CH3:20].[Cl:21][C:22]1[CH:28]=[CH:27][C:25]([NH2:26])=[C:24]([F:29])[CH:23]=1.Cl.N1C=CC=CC=1.C(=O)(O)[O-].[Na+]>C(OCCO)C>[Cl:21][C:22]1[CH:28]=[CH:27][C:25]([NH:26][C:10]2[C:9]3[C:14](=[CH:15][C:6]([O:5][CH2:4][CH2:3][CH2:2][Cl:1])=[C:7]([O:19][CH3:20])[CH:8]=3)[N:13]=[CH:12][C:11]=2[C:16]#[N:17])=[C:24]([F:29])[CH:23]=1

Participants

6

Reactant 4

HCID 938984-Chloro-2-fluoroanilineHCID 516892Sodium BicarbonateHCID 10176127Pyridinium chlorideHCID 112206374-Chloro-7-(3-chloropropoxy)-6-methoxyquinoline-3-carbonitrile

Product 1

HCID 102022744-(4-Chloro-2-fluoro-phenylamino)-7-(3-chloro-propoxy)-6-methoxy-quinoline-3-carbonitrileYield 68.8%

Reagents, catalysts & solvents 1

HCID 8076Glycol monoethyl etherSolvent

Procedure

A mixture of 3.1 g (9.96 mmol) of 7-(3-Chloro-propoxy)-4-chloro-6-methoxy-quinoline-3-carbonitrile, 1.6 g (10.96 mmol) of 4-chloro-2-fluoro-aniline, and 1.2 g (10 mmol) of pyridine hydrochloride in 31 ml of 2-ethoxyethanol was stirred at reflux for 1.5 hr. The mixture was poured into saturated sodium bicarbonate solution and extracted with ethyl acetate. The organic solution was dried and solvent was removed. The residue was purified on a silica gel column eluting with chloroform-ether mixtures to give 2.88 g of the title compound as an off-white solid powder: mass spectrum (electrospray, m/e) M+H 419.7.

Workup

  1. temperatureat reflux for 1.5 hr
  2. extractionextracted with ethyl acetate
  3. customThe organic solution was dried
  4. customsolvent was removed
  5. customThe residue was purified on a silica gel column
  6. washeluting with chloroform-ether mixtures

Sources & evidence

ORD record
ord-64557b9c37064bf08f1f902a6e68d814
Source dataset
uspto-grants-2002_05
Patent number
US06384051B1

Reaction notes

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