2-Chloro-5-((2,2,2-trifluoroacetamido)methyl)benzoyl isocyanate → N-(4-chloro-3-(5-oxo-1-(4-(trifluoromethyl)phenyl)-4,5-dihydro-1H-1,2,4-triazol-3-yl)benzyl)-2,2,2-trifluoroacetamide

HRID 59351Notes

Reaction equation

HRID 59351 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]1[CH:8]=[CH:7][C:6]([NH:9][NH:10]C(OC(C)(C)C)=O)=[CH:5][CH:4]=1.[Cl:20][C:21]1[CH:31]=[CH:30][C:29]([CH2:32][NH:33][C:34](=[O:39])[C:35]([F:38])([F:37])[F:36])=[CH:28][C:22]=1[C:23]([N:25]=[C:26]=[O:27])=O>C(Cl)Cl.C(O)(C(F)(F)F)=O>[Cl:20][C:21]1[CH:31]=[CH:30][C:29]([CH2:32][NH:33][C:34](=[O:39])[C:35]([F:38])([F:37])[F:36])=[CH:28][C:22]=1[C:23]1[NH:25][C:26](=[O:27])[N:9]([C:6]2[CH:7]=[CH:8][C:3]([C:2]([F:1])([F:19])[F:18])=[CH:4][CH:5]=2)[N:10]=1

Participants

5

Reactant 2

HCID 900192862-Chloro-5-((2,2,2-trifluoroacetamido)methyl)benzoyl isocyanateHCID 90019516tert-Butyl 2-(4-(trifluoromethyl)phenyl)hydrazinecarboxylate

Product 1

HCID 136246025N-(4-chloro-3-(5-oxo-1-(4-(trifluoromethyl)phenyl)-4,5-dihydro-1H-1,2,4-triazol-3-yl)benzyl)-2,2,2-trifluoroacetamideYield 41.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of tert-butyl 2-(4-(trifluoromethyl)phenyl)hydrazinecarboxylate (Intermediate-53, 1.00 g, 3.63 mmol) in DCM (20 mL), 2-chloro-5-((2,2,2-trifluoroacetamido)methyl)benzoyl isocyanate (step-3 of Intermediate-26, 1.30 g, 4.03 mmol) was added and the reaction mass was stirred at RT for 2 h. After completion of reaction, excess of solvent was removed under reduced pressure to obtain 0.700 g of the crude product. To a solution of obtained crude product in DCM (5.0 mL), TFA (5.0 mL) was added and the reaction mass was stirred at RT for 2-3 h. Excess of the solvent was removed from the reaction mass under reduced pressure and the reaction mass was quenched in ice and filtered to obtain 0.700 g of the desired title product. 1H NMR (300 MHz, DMSO d6): δ 4.45 (d, 1H), 7.50 (d, J=4.8 Hz, 1H), 7.65-7.68 (m, 2H), 8.85 (d, J=6.6 Hz, 2H), 8.18 (d, J=6.3 Hz, 2H), 10.05 (s, 1H), 12.69 (s, 1H); MS (m/z): 463.17 (M−H)−.

Workup

  1. customAfter completion of reaction
  2. customexcess of solvent was removed under reduced pressure
  3. customto obtain 0.700 g of the crude product
  4. additionwas added
  5. stirringthe reaction mass was stirred at RT for 2-3 h
  6. customExcess of the solvent was removed from the reaction mass under reduced pressure
  7. customthe reaction mass was quenched in ice
  8. filtrationfiltered

Sources & evidence

ORD record
ord-3ed9cb1284744f4485030ba09f523d41
Source dataset
uspto-grants-2016_09
Patent number
US09439890B2

Reaction notes

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