Water → HCID 140661989, compound

HRID 1404869Notes

Reaction equation

HRID 1404869 reaction equation
[CH:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[NH:11][C:12]([NH:14]/[N:15]=[CH:16]/[C:17]1[CH:22]=[CH:21][C:20]([C:23]2[N:27]=[CH:26][N:25]([C:28]3[CH:33]=[CH:32][C:31]([O:34][C:35]([F:38])([F:37])[F:36])=[CH:30][CH:29]=3)[N:24]=2)=[CH:19][CH:18]=1)=[S:13])([CH2:3][CH3:4])[CH3:2].C(N(CC)CC)C.Br[CH2:47][C:48](=[O:53])[C:49]([F:52])([F:51])[F:50].O>CC(=O)CC>[CH:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[C:48]([C:49]([F:52])([F:51])[F:50])([OH:53])[CH2:47][S:13]/[C:12]/1=[N:14]/[N:15]=[CH:16]\[C:17]1[CH:22]=[CH:21][C:20]([C:23]2[N:27]=[CH:26][N:25]([C:28]3[CH:29]=[CH:30][C:31]([O:34][C:35]([F:36])([F:37])[F:38])=[CH:32][CH:33]=3)[N:24]=2)=[CH:19][CH:18]=1)([CH2:3][CH3:4])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 8471Triethylamine2×HCID 790083-Bromo-1,1,1-trifluoro-2-propanone2×HCID 89723792HCID 89723792, compound

Product 1

HCID 140661989HCID 140661989, compoundYield 7%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of (E)-N-(2-(sec-butyl)phenyl)-2-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzylidene)hydrazinecarbothioamide (203 mg, 0.38 mmol) in butanone (3.8 mL) was added triethylamine (0.07 mL, 0.49 mmol) and 3-bromo-1,1,1-trifluoroacetone (0.05 mL, 0.49 mmol), and the reaction was stirred at 85° C. for 20 hours, after which LC/MS analysis showed minimal conversion. Additional triethylamine (0.03 mL, 0.21 mmoL) and 3-bromo-1,1,1-trifluoroacetone (0.1 mL, 0.98 mmol) were added to the reaction mixture and the reaction was stirred at 90° C. for an additional 20 hours. The mixture was allowed to cool to room temperature, transferred to a separatory funnel containing water (5 mL), and extracted twice with dichloromethane. The organic extracts were filtered through a phase separator, adsorbed onto silica gel, and purified by flash chromatography (0-20% ethyl acetate/B, where B=1:1 dichloromethane/hexanes). Further purification by reverse-phase flash chromatography (0-100% acetonitrile/water) provided the title compound as an orange solid (16 mg, 7%): 1H NMR (400 MHz, CDCl3) δ 8.59-8.54 (m, 1H), 8.30-8.13 (m, 3H), 7.79 (dd, J=8.6, 6.7 Hz, 4H), 7.45-7.34 (m, 5H), 7.32-7.21 (m, 1H), 3.99 (s, 1H), 3.83 (d, J=12.2 Hz, 1H), 3.52-3.38 (m, 1H), 2.82-2.75 (m, 1H), 1.27-1.26 (m, 1H), 1.21-1.12 (m, 3H), 0.97-0.75 (m, 4H); 19F NMR (376 MHz, CDCl3) δ −58.03, −78.23, −78.32, −78.76, −78.84; ESIMS m/z 650 (M+H)+.

Workup

  1. stirringthe reaction was stirred at 90° C. for an additional 20 hours
  2. temperatureto cool to room temperature
  3. customtransferred to a separatory funnel
  4. extractionextracted twice with dichloromethane
  5. filtrationThe organic extracts were filtered through a phase separator
  6. custompurified by flash chromatography (0-20% ethyl acetate/B, where B=1:1 dichloromethane/hexanes)
  7. customFurther purification by reverse-phase flash chromatography (0-100% acetonitrile/water)

Sources & evidence

ORD record
ord-967c1840a98841deac3ff43015103263
Source dataset
uspto-grants-2014_12
Patent number
US08916183B2

Reaction notes

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