3-(Trifluoromethyl)aniline → 4-(3-(2-chloro-5-((2,2,2-trifluoroacetamido)methyl)phenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-2-methoxy-N-(3-(trifluoromethyl)phenyl)benzamide

HRID 59270Notes

Reaction equation

HRID 59270 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:10](=[O:15])[C:11]([F:14])([F:13])[F:12])=[CH:4][C:3]=1[C:16]1[NH:20][C:19](=[O:21])[N:18]([C:22]2[CH:31]=[CH:30][C:25]([C:26](OC)=[O:27])=[C:24]([O:32][CH3:33])[CH:23]=2)[N:17]=1.[F:34][C:35]([F:44])([F:43])[C:36]1[CH:37]=[C:38]([CH:40]=[CH:41][CH:42]=1)[NH2:39].C[Al](C)C>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:10](=[O:15])[C:11]([F:12])([F:14])[F:13])=[CH:4][C:3]=1[C:16]1[NH:20][C:19](=[O:21])[N:18]([C:22]2[CH:31]=[CH:30][C:25]([C:26]([NH:39][C:38]3[CH:40]=[CH:41][CH:42]=[C:36]([C:35]([F:34])([F:43])[F:44])[CH:37]=3)=[O:27])=[C:24]([O:32][CH3:33])[CH:23]=2)[N:17]=1

Participants

5

Reactant 3

HCID 73753-(Trifluoromethyl)anilineHCID 16682925TrimethylaluminumHCID 136492408methyl 4-(3-(2-chloro-5-((2,2,2-trifluoroacetamido)methyl)phenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-2-methoxybenzoate

Product 1

HCID 1364924124-(3-(2-chloro-5-((2,2,2-trifluoroacetamido)methyl)phenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-2-methoxy-N-(3-(trifluoromethyl)phenyl)benzamideYield 67.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of methyl 4-(3-(2-chloro-5-((2,2,2-trifluoroacetamido) methyl)phenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-2-methoxybenzoate (0.200 g, 0.413 mmol) in dry toluene (3 mL) was added 3-(trifluoromethyl)aniline (0.100 g, 0.619 mmol) followed by addition of trimethyl aluminium (2M solution in toluene) (2 mL). The reaction mass was refluxed for 3-4 h. The reaction mass was quenched in water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulphate and concentrated to afford 0.170 g of desired product. 1H NMR (300 MHz, DMSO d6): δ 3.95 (s, 3H), 4.46 (d, J=6.0 Hz, 2H), 7.56 (t, J=6.0 Hz, 2H), 7.59-7.85 (m, 6H), 7.96 (d, J=7.8 Hz, 1H), 8.26 (s, 1H), 10.09 (s, 1H), 10.37 (s, 1H), 12.65 (s, 1H); MS (m/z): (M)+ 614.08.

Workup

  1. temperatureThe reaction mass was refluxed for 3-4 h
  2. customThe reaction mass was quenched in water
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer was dried over anhydrous sodium sulphate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-d23c4f0958434363b296943055454be7
Source dataset
uspto-grants-2016_09
Patent number
US09439890B2

Reaction notes

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