1H-1,2,4-Triazole → 3-chloro-N-{4-chloro-2-[(4-chlorophenyl)carbamoyl]phenyl}-4-(1H-1,2,4-triazol-1-ylmethyl)thiophene-2-carboxamide

HRID 2300940Notes

Reaction equation

HRID 2300940 reaction equation
[NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.[H-].[Na+].[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:35])[C:17]2[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:18]=2[NH:24][C:25]([C:27]2[S:28][CH:29]=[C:30]([CH2:33]Cl)[C:31]=2[Cl:32])=[O:26])=[CH:11][CH:10]=1>CN(C=O)C>[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([NH:15][C:16](=[O:35])[C:17]2[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:18]=2[NH:24][C:25]([C:27]2[S:28][CH:29]=[C:30]([CH2:33][N:1]3[CH:5]=[N:4][CH:3]=[N:2]3)[C:31]=2[Cl:32])=[O:26])=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 92571H-1,2,4-TriazoleHCID 24758Sodium hydrideHCID 18376557N-(4-chlorophenyl)-2-[((4-(chloromethyl)-3-chlorothiophen-2-yl)carbonyl)amino]-5-chlorobenzamide

Product 1

HCID 183769763-chloro-N-{4-chloro-2-[(4-chlorophenyl)carbamoyl]phenyl}-4-(1H-1,2,4-triazol-1-ylmethyl)thiophene-2-carboxamideYield 102.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 1,2,4-triazole (0.40 g, 5.7 mmol) in DMF (10 mL) was added NaH (60% dispersion in mineral oil, 0.23 g, 5.7 mmol) and the mixture stirred at ambient temperature. After 10 min, N-(4-chlorophenyl)-2-[((4-(chloromethyl)-3-chlorothiophen-2-yl)carbonyl)amino]-5-chlorobenzamide (0.90 g, 1.9 mmol) in DMF (5 mL) was added and stirring continued. After 18 hours, the mixture was poured onto water and extracted with methylene chloride. The organic layer was dried over MgSO4 and concentrated in vacuo. Purification by flash chromatography on silica gel afforded 0.99 g (77% yield) of N-(4-chlorophenyl)-2-[((3-chloro-4-((1,2,4-triazol-1-yl)methyl)thiophen-2-yl)carbonyl)amino]-5-chlorobenzamide; as a white solid; NMR (DMSO-d6/TFA) 11.2 (s, 1), 10.7 (s, 1), 9.3 (s, 1), 8.5 (s, 1), 8.3 (d, 1), 8.0 (s, 1), 7.9 (d, 1), 7.7 (d, 2), 7.6 (dd, 1), 7.4 (d, 2), 5.5 (s, 2) ppm.

Workup

  1. stirringstirring
  2. waitAfter 18 hours
  3. additionthe mixture was poured onto water
  4. extractionextracted with methylene chloride
  5. dry with materialThe organic layer was dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customPurification by flash chromatography on silica gel

Sources & evidence

ORD record
ord-9ab4d0f26ce042eb841f5beb5769ebce
Source dataset
uspto-grants-2002_12
Patent number
US06498185B1

Reaction notes

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