Pivaloyl chloride → N-(3-(1-(4-(Trifluoromethyl)phenyl)-4,5-dihydro-5-oxo-1H-1,2,4-triazol-3-yl)-2,4-dimethylbenzyl)pivalamide

HRID 59515Notes

Reaction equation

HRID 59515 reaction equation
[NH2:1][CH2:2][C:3]1[C:4]([CH3:26])=[C:5]([C:10]2[NH:11][C:12](=[O:25])[N:13]([C:15]3[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=3)[N:14]=2)[C:6]([CH3:9])=[CH:7][CH:8]=1.[C:27](Cl)(=[O:32])[C:28]([CH3:31])([CH3:30])[CH3:29]>C1COCC1>[F:22][C:21]([F:23])([F:24])[C:18]1[CH:19]=[CH:20][C:15]([N:13]2[C:12](=[O:25])[NH:11][C:10]([C:5]3[C:4]([CH3:26])=[C:3]([CH:8]=[CH:7][C:6]=3[CH3:9])[CH2:2][NH:1][C:27](=[O:32])[C:28]([CH3:31])([CH3:30])[CH3:29])=[N:14]2)=[CH:16][CH:17]=1

Participants

4

Reactant 2

HCID 62493Pivaloyl chlorideHCID 1364924295-(3-(Aminomethyl)-2,6-dimethylphenyl)-2-(4-(trifluoromethyl)phenyl)-2H-1,2,4-triazol-3(4H)-one

Product 1

HCID 136246059N-(3-(1-(4-(Trifluoromethyl)phenyl)-4,5-dihydro-5-oxo-1H-1,2,4-triazol-3-yl)-2,4-dimethylbenzyl)pivalamideYield 19.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 5-(3-(aminomethyl)-2,6-dimethylphenyl)-2-(4-(trifluoromethyl)phenyl)-2H-1,2,4-triazol-3(4H)-one (Intermediate-66, 0.050 g) in dry THF (5 mL), TEA (3 mL) was added and stirred the reaction mixture for 20 minutes. The reaction mixture was cooled to 0° C. and pivaloyl chloride (0.05 g, 0.563 mmol) was added and stirred for 3 h at RT. After completion of the reaction, the reaction mass was quenched with water, extracted with DCM:MeOH. The organic layer was separated, concentrated, and purified by column chromatography to afford 0.012 g of the desired title product. 1H NMR (400 MHz, DMSO d6): δ 1.15 (s, 9H), 2.18 (s, 3H), 2.22 (s, 3H), 4.24 (d, J=12.6 Hz, 2H), 7.19 (d, 1H), 7.25 (d, 1H), 7.84 (d, J=5.7 Hz, 2H), 8.0 (t, 1H), 8.20 (d, J=6.4 Hz, 2H), 12.30 (br s, 1H); MS (m/z): 447.20 (M+H)+.

Workup

  1. stirringstirred for 3 h at RT
  2. customAfter completion of the reaction
  3. customthe reaction mass was quenched with water
  4. extractionextracted with DCM
  5. customThe organic layer was separated
  6. concentrationconcentrated
  7. custompurified by column chromatography

Sources & evidence

ORD record
ord-7dbac8e56cf64536ae4db07b1250ce6a
Source dataset
uspto-grants-2016_09
Patent number
US09439890B2

Reaction notes

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