Water → HCID 140661988, compound

HRID 1404868Notes

Reaction equation

HRID 1404868 reaction equation
[CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[NH:10][C:11]([NH:13]/[N:14]=[CH:15]/[C:16]1[CH:21]=[CH:20][C:19]([C:22]2[N:26]=[CH:25][N:24]([C:27]3[CH:32]=[CH:31][C:30]([O:33][C:34]([F:37])([F:36])[F:35])=[CH:29][CH:28]=3)[N:23]=2)=[CH:18][CH:17]=1)=[S:12])([CH3:3])[CH3:2].Br[CH2:39][C:40](=[O:45])[C:41]([F:44])([F:43])[F:42].C(N(CC)CC)C.O>CC(=O)CC>[CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[N:10]1[C:40]([C:41]([F:44])([F:43])[F:42])([OH:45])[CH2:39][S:12]/[C:11]/1=[N:13]/[N:14]=[CH:15]\[C:16]1[CH:17]=[CH:18][C:19]([C:22]2[N:26]=[CH:25][N:24]([C:27]3[CH:28]=[CH:29][C:30]([O:33][C:34]([F:37])([F:35])[F:36])=[CH:31][CH:32]=3)[N:23]=2)=[CH:20][CH:21]=1)([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 790083-Bromo-1,1,1-trifluoro-2-propanoneHCID 885903141-(2-propan-2-ylphenyl)-3-[(E)-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]methylideneamino]thiourea

Product 1

HCID 140661988HCID 140661988, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of (E)-N-(2-isopropylphenyl)-2-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzylidene)hydrazinecarbothioamide (351 mg, 0.67 mmol) in butanone (6.7 mL) was added 3-bromo-1,1,1-trifluoroacetone (0.14 mL, 1.34 mmol) and triethylamine (0.19 mL, 1.34 mmol), and the reaction was stirred at 85° C. for 21 hours. The mixture was allowed to cool to room temperature, transferred to a separatory funnel containing water (5 mL), and the aqueous mixture 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) to provide a diastereomeric mixture (2:1) of the title compound as an orange solid (189 mg, 45%): mp 185-187° C.; 1H NMR (400 MHz, CDCl3, both diastereomers) δ 8.56 (m, 2H), 8.22-8.14 (m, 6H), 7.83-7.75 (m, 8H), 7.49-7.34 (m, 10H), 7.32-7.23 (m, 2H), 4.22 (s, 1H), 3.82 (dd, J=12.5, 4.8 Hz, 2H), 3.51 (d, J=13.2 Hz, 1H), 3.40 (d, J=12.3 Hz, 1H), 3.31 (s, 1H), 3.09 (tt, J=13.9, 7.0 Hz, 2H), 1.31-1.13 (m, 12H); 19F NMR (376 MHz, CDCl3) δ −58.02, −78.33, −78.77; ESIMS m/z 636 (M+H)+.

Workup

  1. temperatureto cool to room temperature
  2. customtransferred to a separatory funnel
  3. extractionthe aqueous mixture extracted twice with dichloromethane
  4. filtrationThe organic extracts were filtered through a phase separator
  5. custompurified by flash chromatography (0-20% ethyl acetate/B, where B=1:1 dichloromethane/hexanes)

Sources & evidence

ORD record
ord-801bd098446948fbb12d8e37f5fa8440
Source dataset
uspto-grants-2014_12
Patent number
US08916183B2

Reaction notes

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