Methylhydrazine → 3-(2-Chloro-6-fluorophenyl)-1-methyl-5-(4-methyl-3-thienyl)-1H-1,2,4-triazole

HRID 1828021Notes

Reaction equation

HRID 1828021 reaction equation
[CH3:1][NH:2][NH2:3].[Cl:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:6]=1[C:12](SC)=[N:13][C:14]([C:16]1[C:20]([CH3:21])=[CH:19][S:18][CH:17]=1)=O>C1(C)C=CC=CC=1>[Cl:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:6]=1[C:12]1[N:13]=[C:14]([C:16]2[C:20]([CH3:21])=[CH:19][S:18][CH:17]=2)[N:2]([CH3:1])[N:3]=1

Participants

4

Reactant 2

HCID 6061Methylhydrazine2×HCID 20872842HCID 20872842, compound

Product 1

HCID 220651003-(2-Chloro-6-fluorophenyl)-1-methyl-5-(4-methyl-3-thienyl)-1H-1,2,4-triazoleYield 84%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Conditions

Temperature
80 °C

Procedure

A solution of methylhydrazine (2.02 mL, 1.75 g, 38 mmol) in toluene (5 mL) was added at a rapid dropwise rate to a solution of methyl 2-chloro-6-fluoro-N-[(4-methylthien-3-yl)carbonyl]benzenecarbimidothioate (4.15 g, 12.7 mmol) in dry toluene (100 mL) at 55° C. The reaction was stirred at this temperature for 10 minutes and then left at room temperature for 14 hours. Another identical portion of methylhydrazine in toluene was added at room temperature and the reaction was heated at 80° C. for 3 hours and refluxed for an additional 3 hours. After cooling to room temperature, the reaction mixture was washed with water (100 mL), dilute hydrochloric acid (0.05 N, 2×100 mL) and brine (70 mL), dried over magnesium sulphate and concentrated under reduced pressure. The residue was recrystallised from ethyl acetate/hexane to give white cubes. The mother liquor was chromatographed (eluant, 30:9:1 hexane/methylene chloride/acetonitrile to afford the product (3.25 g, 84%): mp 153–155° C.; 1H NMR (CDCl3) δ 7.54 (d, 1H), 7.26–7.38 (m, 2H), 7.06–7.13 (m, 2H), 3.98 (s, 3H), 2.35 (d, 3H); 19F NMR (external reference)—110 ppm; EI/MS 307 m/e (M−1).

Workup

  1. waitleft at room temperature for 14 hours
  2. temperaturerefluxed for an additional 3 hours
  3. temperatureAfter cooling to room temperature
  4. washthe reaction mixture was washed with water (100 mL), dilute hydrochloric acid (0.05 N, 2×100 mL) and brine (70 mL)
  5. dry with materialdried over magnesium sulphate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was recrystallised from ethyl acetate/hexane
  8. customto give white cubes
  9. customThe mother liquor was chromatographed (eluant, 30:9:1 hexane/methylene chloride/acetonitrile

Sources & evidence

ORD record
ord-dd96b6fde82949759d3d46785bcee138
Source dataset
uspto-grants-2006_06
Patent number
US07056940B2

Reaction notes

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