Methylamine → 4-Chloro-N,2,6-trimethyl-pyridine-3-carboxamide

HRID 333964Notes

Reaction equation

HRID 333964 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([CH3:9])[C:3]=1[C:10]([OH:12])=O.C(Cl)(=O)C(Cl)=O.[CH3:19][NH2:20].C1COCC1>ClCCl.CN(C=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([CH3:9])[C:3]=1[C:10]([NH:20][CH3:19])=[O:12]

Participants

7

Reactant 4

HCID 6329MethylamineHCID 8028TetrahydrofuranHCID 65578Oxalyl chlorideHCID 52391234-Chloro-2,6-dimethyl-nicotinic acid

Product 1

HCID 668359274-Chloro-N,2,6-trimethyl-pyridine-3-carboxamideYield 62%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

4-Chloro-2,6-dimethyl-pyridine-3-carboxylic acid (925 mg, 5 mmol) was suspended in anhydrous dichloromethane (15 ml), the mixture was cooled to 0° C. and oxalyl chloride (560 μl, 6.5 mmol) was added dropwise with stirring followed by two drops of DMF. The mixture was stirred at room temperature for 90 minutes, the solvent was removed under reduced pressure, the residue was dissolved in anhydrous dichloromethane (15 ml), the solution was evaporated to dryness again, and the residue was dissolved in anhydrous dichloromethane (15 ml) and cooled to 0° C. TEA (2.1 ml, 15 mmol) was added dropwise followed by dropwise addition of a 2M solution of methylamine in THF (5 ml, 10 mmol). The mixture was stirred at 0° C. for 30 minutes, the solvent was removed under reduced pressure and the residue taken up in saturated sodium bicarbonate solution (40 ml). The mixture was extracted with dichloromethane (3×), the combined extracts were dried over sodium sulfate, the solvent was evaporated under reduced pressure and the residue was triturated with diethylether to yield 610 mg of a crystalline solid (3.1 mmol, 62%). MS (APCI): m/z=198.8 [M+1]+.

Workup

  1. stirringThe mixture was stirred at room temperature for 90 minutes
  2. customthe solvent was removed under reduced pressure
  3. dissolutionthe residue was dissolved in anhydrous dichloromethane (15 ml)
  4. customthe solution was evaporated to dryness again
  5. dissolutionthe residue was dissolved in anhydrous dichloromethane (15 ml)
  6. temperaturecooled to 0° C
  7. stirringThe mixture was stirred at 0° C. for 30 minutes
  8. customthe solvent was removed under reduced pressure
  9. extractionThe mixture was extracted with dichloromethane (3×)
  10. dry with materialthe combined extracts were dried over sodium sulfate
  11. customthe solvent was evaporated under reduced pressure
  12. customthe residue was triturated with diethylether

Sources & evidence

ORD record
ord-e49a35f7cf9d4f239d8d6dbcbbb8f440
Source dataset
uspto-grants-2014_11
Patent number
US08883791B2

Reaction notes

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