Sodium hydride → 3-(2-Chloro-6-fluorophenyl)-1-(4-(3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl)-3-methoxyphenyl)-1H-1,2,4-triazol-5(4H)-one

HRID 59455

Reaction equation

HRID 59455 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][C:5]([C:6](=[N:8][OH:9])[NH2:7])=[CH:4][CH:3]=1.[H-].[Na+].[Cl:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:16]=1[C:22]1[NH:26][C:25](=[O:27])[N:24]([C:28]2[CH:37]=[CH:36][C:31]([C:32](OC)=O)=[C:30]([O:38][CH3:39])[CH:29]=2)[N:23]=1>C1(C)C=CC=CC=1>[Cl:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:16]=1[C:22]1[NH:26][C:25](=[O:27])[N:24]([C:28]2[CH:37]=[CH:36][C:31]([C:32]3[O:9][N:8]=[C:6]([C:5]4[CH:10]=[CH:11][C:2]([Cl:1])=[CH:3][CH:4]=4)[N:7]=3)=[C:30]([O:38][CH3:39])[CH:29]=2)[N:23]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2246504-chloro-N'-hydroxybenzenecarboximidamideHCID 136492448methyl 4-(3-(2-chloro-6-fluorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-2-methoxybenzoate

Product 1

HCID 1366125233-(2-Chloro-6-fluorophenyl)-1-(4-(3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl)-3-methoxyphenyl)-1H-1,2,4-triazol-5(4H)-oneYield 11.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 4-chloro-N′-hydroxybenzimidamide (Intermediate-19, 0.069 g, 0.39 mmol) in dry toluene was added sodium hydride (0.016 g, 0.39 mmol). The reaction mixture was refluxed for 30 minutes followed by addition of methyl 4-(3-(2-chloro-6-fluorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-2-methoxybenzoate (step-2 of Intermediate-15, 0.100 g, 0.26 mmol). The reaction mixture was refluxed for 5-6 h. The reaction mixture was quenched in water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulphate and concentrated to afford crude product which was further purified by column chromatography to afford 0.015 g of desired product. 1H NMR (DMSO-d6): δ 3.98 (s, 3H), 7.45-7.48 (m, 1H), 7.54 (d, J=8.1 Hz, 1H), 7.67 (d, J=8.4 Hz, 3H), 7.83 (d, J=8.1 Hz, 1H), 7.95 (s, 1H), 8.10 (d, J=8.4 Hz, 2H), 8.18 (d, J=8.7 Hz, 1H), 12.90 (br s, 1H). MS [M+H]+: 499.89.

Workup

  1. temperatureThe reaction mixture was refluxed for 30 minutes
  2. temperatureThe reaction mixture was refluxed for 5-6 h
  3. customThe reaction mixture was quenched in water
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic layer was dried over anhydrous sodium sulphate
  6. concentrationconcentrated
  7. customto afford crude product which
  8. customwas further purified by column chromatography

Sources & evidence

ORD record
ord-019c3838a7324a1ab4c029ed11690aa4
Source dataset
uspto-grants-2016_09
Patent number
US09439890B2

Linked notes

Loading…