1H-1,2,4-Triazole → TAK-603

HRID 1940171Notes

Reaction equation

HRID 1940171 reaction equation
[NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.[H-].[Na+].Cl[CH2:9][C:10]1[C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[C:18]([C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[C:27]([O:33][CH3:34])[CH:26]=2)[C:17]2[C:12](=[CH:13][C:14]([O:37][CH3:38])=[C:15]([O:35][CH3:36])[CH:16]=2)[N:11]=1>CN(C)C=O.O>[CH3:34][O:33][C:27]1[CH:26]=[C:25]([C:18]2[C:17]3[C:12](=[CH:13][C:14]([O:37][CH3:38])=[C:15]([O:35][CH3:36])[CH:16]=3)[N:11]=[C:10]([CH2:9][N:1]3[CH:5]=[N:4][CH:3]=[N:2]3)[C:19]=2[C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:30]=[CH:29][C:28]=1[O:31][CH3:32]

Participants

6

Reactant 3

HCID 92571H-1,2,4-TriazoleHCID 24758Sodium hydrideHCID 10813243Ethyl 2-chloromethyl-4-(3,4-dimethoxyphenyl)-6,7-dimethoxyquinoline-3-carboxylate

Product 1

HCID 153980TAK-603Yield 53%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1H-1,2,4-triazole (0.558 g) in N,N-dimethylformamide (30 ml) was added sodium hydride in oil and the mixture was stirred at room temperature for 15 minutes. Then, ethyl 2-chloromethyl-4-(3,4-dimethoxyphenyl)-6,7-dimethoxyquinoline-3-carboxylate (3.0 g) was added. The mixture was stirred at 80° C. for 1 hour, after which it was poured in water and extracted with ethyl acetate. The ethyl acetate layer was washed with water and dried (MgSO4) and the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography. Form the first eluate with chloroform-methanol (40:1, v/v), ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2,4-triazol-1-ylmethyl)quinoline-3-carboxylate (1.7 g, 53%) was obtained. Recrystallization from ethyl acetate-hexane provided colorless prisms, m.p. 176°-177° C.

Workup

  1. stirringThe mixture was stirred at 80° C. for 1 hour
  2. extractionextracted with ethyl acetate
  3. washThe ethyl acetate layer was washed with water
  4. dry with materialdried (MgSO4)
  5. distillationthe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-e6fcf4ad9d214dcea3ae1d4c70004d0e
Source dataset
uspto-grants-1997_12
Patent number
US05698699

Reaction notes

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