Lawesson's reagent → 2-(5-(3-Amino-5-(trifluoromethyl)pyridin-2-yl)-1,3,4-thiadiazol-2-yl)-1,1,1-trifluoropropan-2-ol

HRID 574217Notes

Reaction equation

HRID 574217 reaction equation
[NH2:1][C:2]1[C:3]([C:12]([NH:14][NH:15][C:16](=O)[C:17]([OH:23])([CH3:22])[C:18]([F:21])([F:20])[F:19])=O)=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:34])=CC=1>C1(C)C=CC=CC=1.O>[NH2:1][C:2]1[C:3]([C:12]2[S:34][C:16]([C:17]([OH:23])([CH3:22])[C:18]([F:21])([F:20])[F:19])=[N:15][N:14]=2)=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1

Participants

5

Reactant 2

HCID 87949Lawesson's reagentHCID 867296043-Amino-N'-(3,3,3-trifluoro-2-hydroxy-2-methylpropanoyl)-5-(trifluoromethyl) picolinohydrazide

Product 1

HCID 715157562-(5-(3-Amino-5-(trifluoromethyl)pyridin-2-yl)-1,3,4-thiadiazol-2-yl)-1,1,1-trifluoropropan-2-ol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture comprising 3-amino-N′-(3,3,3-trifluoro-2-hydroxy-2-methylpropanoyl)-5-(trifluoromethyl) picolinohydrazide (184 mg, 0.511 mmol) in toluene (5.108 ml) was treated with Lawesson reagent (310 mg, 0.766 mmol) and heated at reflux for 1 h. The reaction mixture was diluted with water and extracted with EtOAc. The combined organic extracts were washed saturated sodium bicarbonate solution, brine, dried (phase separator) and concentrated in vacuo. Purification by chromatography on silica eluting with 0-30% EtOAc in iso-hexane afforded an orange gum. Further purification was carried out by preparative reverse phase HPLC eluting with 30-70% MeCN in water (0.1% TFA) to afford the title compound; 1H NMR (400 MHz, DMSO-d6) δ 8.2 (1H, s), 8.0 (1H, s), 7.6 (1H, s), 7.4 (2H, s), 1.9 (3H, s). LC-MS Rt=4.03 min [M+H]+ 359.4 Method 10minLC_v003.

Workup

  1. temperatureheated
  2. temperatureat reflux for 1 h
  3. extractionextracted with EtOAc
  4. washThe combined organic extracts were washed saturated sodium bicarbonate solution, brine
  5. customdried (phase separator)
  6. concentrationconcentrated in vacuo
  7. customPurification by chromatography on silica eluting with 0-30% EtOAc in iso-hexane
  8. customafforded an orange gum
  9. customFurther purification
  10. washeluting with 30-70% MeCN in water (0.1% TFA)

Sources & evidence

ORD record
ord-0c35a40124ec49399b7c1efe7f486b2d
Source dataset
uspto-grants-2015_05
Patent number
US09034879B2

Reaction notes

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