Hydrogen Sulfide → 1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinecarbothioamide

HRID 1023022Notes

Reaction equation

HRID 1023022 reaction equation
[SH2:1].[CH3:2][C:3]1[N:7]([CH2:8][C:9]([N:11]2[CH2:16][CH2:15][CH:14]([C:17]#[N:18])[CH2:13][CH2:12]2)=[O:10])[N:6]=[C:5]([C:19]([F:22])([F:21])[F:20])[CH:4]=1.N(CCO)CCO>CN(C)C=O>[CH3:2][C:3]1[N:7]([CH2:8][C:9]([N:11]2[CH2:16][CH2:15][CH:14]([C:17](=[S:1])[NH2:18])[CH2:13][CH2:12]2)=[O:10])[N:6]=[C:5]([C:19]([F:22])([F:20])[F:21])[CH:4]=1

Participants

5

Reactant 3

HCID 402Hydrogen Sulfide3×HCID 8113DiethanolamineHCID 674706371-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinecarbonitrile

Product 1

HCID 580788971-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinecarbothioamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

Hydrogen sulfide gas was passed into a solution of 1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinecarbonitrile (i.e. the product of Example 1, Step B) (9.0 g, 30 mmol) and diethanolamine (3.15 g, 30 mmol) in N,N-dimethylformamide (15 mL) at 50° C. in a flask equipped with dry-ice condenser. The hydrogen sulfide feed was stopped when the reaction mixture became saturated with hydrogen sulfide, as indicated by condensation on the cold-finger. The reaction mixture was stirred for an additional 30 minutes at 50° C. Then excess hydrogen sulfide gas was sparged into the scrubber by a subsurface nitrogen flow, and water (70 mL) was gradually added. The reaction mixture was cooled to 5° C., filtered, and washed with water (2×30 mL). The filter cake was dried at 50° C. in a vacuum-oven to give 8.0 g of the title compound as a solid, melting at 185-186° C.

Workup

  1. customat 50° C.
  2. customequipped with dry-ice condenser
  3. customas indicated by condensation on the cold-finger
  4. customThen excess hydrogen sulfide gas was sparged into the scrubber by a subsurface nitrogen flow, and water (70 mL)
  5. additionwas gradually added
  6. temperatureThe reaction mixture was cooled to 5° C.
  7. filtrationfiltered
  8. washwashed with water (2×30 mL)
  9. customThe filter cake was dried at 50° C. in a vacuum-oven

Sources & evidence

ORD record
ord-4e9497dedb4b4ca9825c5a599a335c62
Source dataset
uspto-grants-2014_05
Patent number
US08722678B2

Reaction notes

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