3,4,5-Trimethoxyaniline → HCID 23498072, compound

HRID 1837338Notes

Reaction equation

HRID 1837338 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([F:14])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:15]#[N:16].[CH3:17][O:18][C:19]1[CH:20]=[C:21]([CH:23]=[C:24]([O:28][CH3:29])[C:25]=1[O:26][CH3:27])[NH2:22].Cl.N1C=CC=CC=1.C(=O)(O)[O-].[Na+]>C(OCCO)C>[F:14][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH:22][C:21]3[CH:23]=[C:24]([O:28][CH3:29])[C:25]([O:26][CH3:27])=[C:19]([O:18][CH3:17])[CH:20]=3)=[C:3]([C:15]#[N:16])[CH:4]=[N:5]2)=[CH:10][C:9]=1[O:12][CH3:13]

Participants

6

Reactant 4

HCID 322853,4,5-TrimethoxyanilineHCID 516892Sodium BicarbonateHCID 10176127Pyridinium chlorideHCID 121507034-Chloro-7-fluoro-6-methoxy-3-quinolinecarbonitrile

Product 1

HCID 23498072HCID 23498072, compoundYield 63.3%

Reagents, catalysts & solvents 1

HCID 8076Glycol monoethyl etherSolvent

Procedure

A mixture of 4-chloro-7-fluoro-6-methoxy-3-quinolinecarbonitrile (500 mg, 2.11 mmol), 3,4,5-trimethoxyaniline (515 mg, 2.81 mmol) and pyridine hydrochloride (270 mg , 2.33 mmol) in 20 mL of 2-ethoxyethanol is heated at reflux for 4 hours then cooled to room temperature. The reaction mixture is poured into aqueous sodium bicarbonate and stirred at room temperature for 15 minutes. The solid is collected by filtration and partitioned between water and ethyl acetate. The organic layer is dried over magnesium sulfate, filtered and concentrated in vacuo. Trituration of the residue with ethyl acetate and diethyl ether provides 512 mg of 7-fluoro-6-methoxy-4-[(3,4,5-trimethoxyphenyl)amino]-3-quinolinecarbonitrile, mp 215-217° C.

Workup

  1. temperatureis heated
  2. temperatureat reflux for 4 hours
  3. filtrationThe solid is collected by filtration
  4. custompartitioned between water and ethyl acetate
  5. dry with materialThe organic layer is dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-eae2fb59986949a9a47943bc2066899a
Source dataset
uspto-grants-2004_08
Patent number
US06780996B2

Reaction notes

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