N-(4-fluoro-phenyl)-N-pyridin-2-ylmethyl-6-chloro-nicotinamide → Thionicotinamide

HRID 404760

Reaction equation

HRID 404760 reaction equation
FC1C=CC([N:8](CC2C=CC=CN=2)[C:9](=O)[C:10]2[CH:15]=[CH:14][C:13](Cl)=[N:12][CH:11]=2)=CC=1.[SH2:25].[Na]>CN(C)C=O.C(OCC)(=O)C>[C:9]([NH2:8])(=[S:25])[C:10]1[CH:15]=[CH:14][CH:13]=[N:12][CH:11]=1

Participants

5

Reactant 2

HCID 59446415N-(4-fluoro-phenyl)-N-pyridin-2-ylmethyl-6-chloro-nicotinamideHCID 86586439Sodium hydrogen sulphide

Product 1

HCID 737155ThionicotinamideYield 82%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a round bottom flask, N-(4-fluoro-phenyl)-N-pyridin-2-ylmethyl-6-chloro-nicotinamide intermediate X (1.078 g, 3.16 mmol) and anhydrous sodium hydrogen sulfide (0.354 g, 6.32 mmol) was suspended in anhydrous dimethylformamide (10 mL). The suspension was heated to reflux, and the reaction mixture turned a deep green color. After 1 h, the reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (20 mL). The aqueous layer was back extracted with ethyl acetate (2×20 ml), and the organic layers combined and washed with saturated aqueous sodium chloride, dried over sodium sulfate, filtered and evaporated by rotary evaporation to yield 0.88 g (82%) of thionicotinamide intermediate XI as a dark yellow oil. TLC (EtOAc/hexanes, 2:1) Rf=0.1; ESI-MS m/z=339.9 [M+H]+.

Workup

  1. temperatureThe suspension was heated
  2. temperatureto reflux
  3. washwashed with water (20 mL)
  4. extractionThe aqueous layer was back extracted with ethyl acetate (2×20 ml)
  5. washwashed with saturated aqueous sodium chloride
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated by rotary evaporation

Sources & evidence

ORD record
ord-afd7bf82aaee4c1693024db9f017b9ce
Source dataset
uspto-grants-2014_06
Patent number
US08748623B2

Linked notes

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