(2-Thienylmethyl)amine → 2,6-difluoro-N-(thiophen-2-ylmethyl)-nicotinamide

HRID 2044179Notes

Reaction equation

HRID 2044179 reaction equation
[F:1][C:2]1[N:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[S:12]1[CH:16]=[CH:15][CH:14]=[C:13]1[CH2:17][NH2:18].CCCCCC.CC(=O)OCC>S(Cl)(Cl)=O>[F:1][C:2]1[N:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([NH:18][CH2:17][C:13]1[S:12][CH:16]=[CH:15][CH:14]=1)=[O:6]

Participants

5

Reactant 3

HCID 34005(2-Thienylmethyl)amineHCID 105830702,6-Difluoropyridine-3-carboxylic acidHCID 21226206Ethyl acetate hexane

Product 1

HCID 671345172,6-difluoro-N-(thiophen-2-ylmethyl)-nicotinamideYield 48%

Reagents, catalysts & solvents 1

HCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
80 °C

Procedure

795 mg (5.0 mmol) of 2,6-difluoro-nicotinic acid were dissolved in thionyl chloride (15 ml) and the solution was heated for 2 h at 80° C. Concentration in vacuo was then carried out and the residue was taken up in dioxane (15 ml). 566 mg (5.0 mmol) of thiophen-2-yl-methanamine were then added and the mixture was stirred for 1 h at RT. Concentration in vacuo was then carried out and the residue was taken up in EA, washed with water, a sat. aq. Na2CO3 sol., water again and brine, dried over Na2SO4, filtered and concentrated in vacuo. CC (hexane/EA 7:3) of the residue yielded 605 mg (2.4 mmol, 48%) of 2,6-difluoro-N-(thiophen-2-ylmethyl)nicotinamide.

Workup

  1. concentrationConcentration in vacuo
  2. concentrationConcentration in vacuo
  3. washwashed with water
  4. dry with materiala sat. aq. Na2CO3 sol., water again and brine, dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-49971231bde846d9adab98bffe7400e2
Source dataset
uspto-grants-2013_11
Patent number
US08586755B2

Reaction notes

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