Water → HCID 140661996, compound

HRID 1404865Notes

Reaction equation

HRID 1404865 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH:9][C:10]([NH:12]/[N:13]=[CH:14]/[C:15]1[CH:20]=[CH:19][C:18]([C:21]2[N:25]=[CH:24][N:23]([C:26]3[CH:31]=[CH:30][C:29]([O:32][C:33]([F:36])([F:35])[F:34])=[CH:28][CH:27]=3)[N:22]=2)=[CH:17][CH:16]=1)=[S:11].C(N(CC)CC)C.Cl[CH2:45][C:46](=[O:48])[CH3:47].O>CC(=O)CC>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[N:9]1[C:46]([CH3:47])([OH:48])[CH2:45][S:11]/[C:10]/1=[N:12]/[N:13]=[CH:14]\[C:15]1[CH:20]=[CH:19][C:18]([C:21]2[N:25]=[CH:24][N:23]([C:26]3[CH:31]=[CH:30][C:29]([O:32][C:33]([F:35])([F:34])[F:36])=[CH:28][CH:27]=3)[N:22]=2)=[CH:17][CH:16]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6571ChloroacetoneHCID 8471TriethylamineHCID 88590284HCID 88590284, compound

Product 1

HCID 140661996HCID 140661996, compoundYield 88.1%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (E)-N-(2,6-difluorophenyl)-2-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzylidene)hydrazinecarbothioamide (253 mg, 0.49 mmol) in butanone (4.9 mL) was added triethylamine (0.14 mL, 0.98 mmol) and chloroacetone (0.055 mL, 0.68 mmol), and the reaction was stirred at 80° C. for 15 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) to afford the title compound as a yellow solid (248 mg, 88%): mp 105° C. (dec); 1H NMR (400 MHz, CDCl3) δ 8.57 (s, 1H), 8.25-8.12 (m, 3H), 7.88-7.72 (m, 4H), 7.39 (d, J=8.5 Hz, 3H), 7.06 (td, J=8.9, 4.4 Hz, 2H), 3.58 (d, J=11.5 Hz, 1H), 3.37 (d, J=11.5 Hz, 1H), 3.24 (d, J=2.7 Hz, 1H), 1.59 (s, 3H); 19F NMR (376 MHz, CDCl3) δ −58.02, −113.71, −115.83, −115.84; ESIMS m/z 576 (M+H)+.

Workup

  1. temperatureto cool to room temperature
  2. customtransferred to a separatory funnel
  3. extractionextracted 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-19e7c6ff8aa34b1ab8ed76a54f38f681
Source dataset
uspto-grants-2014_12
Patent number
US08916183B2

Reaction notes

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