Methanol → 6-Amino-4-(3-chloro-4-fluoro-phenylamino)-7-methoxy-quinoline-3-carbonitrile

HRID 612130Notes

Reaction equation

HRID 612130 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:23][CH3:24])=[C:17]([N+:20]([O-])=O)[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:25]#[N:26])[CH:5]=[CH:6][C:7]=1[F:8].[Cl-].[NH4+].CO>O.C(OCC)(=O)C.[Fe]>[NH2:20][C:17]1[CH:18]=[C:19]2[C:14](=[CH:15][C:16]=1[O:23][CH3:24])[N:13]=[CH:12][C:11]([C:25]#[N:26])=[C:10]2[NH:9][C:4]1[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Cl:1])[CH:3]=1

Participants

7

Reactant 3

HCID 887MethanolHCID 25517Ammonium ChlorideHCID 108940424-(3-Chloro-4-fluoro-phenylamino)-7-methoxy-6-nitro-quinoline-3-carbonitrile

Product 1

HCID 111424366-Amino-4-(3-chloro-4-fluoro-phenylamino)-7-methoxy-quinoline-3-carbonitrileYield 75.9%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4.88 g (13 mmol) of 4-[(3-chloro-4-fluorophenyl)amino]-7-methoxy-6-nitro-quinoline-3-carbonitrile, 5.2 g (97.5 mmol) of ammonium chloride, and 3.3 g (58.5 mmol) iron was stirred at reflux in 60 ml of water and 60 ml of methanol for 4.5 hours. The mixture was diluted with 500 ml of hot ethyl acetate and the hot mixture was filtered. The filtration was washed with saturated sodium chloride solution and then the organic layer was dried over sodium sulfate. The solvent was removed and the residue was chromatographed on silica gel eluting with mixture of ethyl acetate and methanol to give 3.38 g of yellow solid: mass spectrum (electrospray, m/e): M+H 343.4.

Workup

  1. filtrationthe hot mixture was filtered
  2. filtrationThe filtration
  3. washwas washed with saturated sodium chloride solution
  4. dry with materialthe organic layer was dried over sodium sulfate
  5. customThe solvent was removed
  6. customthe residue was chromatographed on silica gel eluting with mixture of ethyl acetate and methanol

Sources & evidence

ORD record
ord-68e358c081864984bb17ed2a72225f4a
Source dataset
uspto-grants-1999_12
Patent number
US06002008

Reaction notes

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