Benzyl Alcohol → 7-Benzyloxy-4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-3-quinolinecarbonitrile

HRID 1837356Notes

Reaction equation

HRID 1837356 reaction equation
[H-].[Na+].[CH2:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[Cl:11][C:12]1[CH:17]=[C:16]([Cl:18])[C:15]([O:19][CH3:20])=[CH:14][C:13]=1[NH:21][C:22]1[C:31]2[C:26](=[CH:27][C:28](F)=[C:29]([O:32][CH3:33])[CH:30]=2)[N:25]=[CH:24][C:23]=1[C:35]#[N:36].C(=O)(O)[O-].[Na+]>CS(C)=O>[CH2:3]([O:10][C:28]1[CH:27]=[C:26]2[C:31]([C:22]([NH:21][C:13]3[CH:14]=[C:15]([O:19][CH3:20])[C:16]([Cl:18])=[CH:17][C:12]=3[Cl:11])=[C:23]([C:35]#[N:36])[CH:24]=[N:25]2)=[CH:30][C:29]=1[O:32][CH3:33])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 114861534-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile

Product 1

HCID 117548757-Benzyloxy-4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-3-quinolinecarbonitrileYield 73.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a mixture of sodium hydride (122 mg, 3.04 mmol) in 6 mL of dimethylsulfoxide is added benzyl alcohol (91 mg, 0.84 mmol). The solution is stirred at room temperature for 40 minutes. 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile (300 mg, 0.76 mmol) is added and the reaction mixture is heated at 100° C. for 3 hours then cooled to room temperature and allowed to stir overnight. The reaction mixture is poured into saturated sodium bicarbonate and the solids are collected by filtration. Purification by flash column chromatography eluting with 10% ethyl acetate in dichloromethane provides 267 mg of 7-benzyloxy-4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-3-quinolinecarbonitrile, mp 198-200° C.

Workup

  1. temperaturethe reaction mixture is heated at 100° C. for 3 hours
  2. temperaturethen cooled to room temperature
  3. stirringto stir overnight
  4. filtrationthe solids are collected by filtration
  5. customPurification by flash column chromatography
  6. washeluting with 10% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-4b349f6a9c0f41b6b668137a6d581729
Source dataset
uspto-grants-2004_08
Patent number
US06780996B2

Reaction notes

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