Methylamine → 2-Chloro-N-methylnicotinamide

HRID 1986101Notes

Reaction equation

HRID 1986101 reaction equation
CN.[CH2:3]([N:5](CC)CC)C.[Cl:10][C:11]1[N:19]=[CH:18][CH:17]=[CH:16][C:12]=1[C:13](Cl)=[O:14]>CC#N>[Cl:10][C:11]1[N:19]=[CH:18][CH:17]=[CH:16][C:12]=1[C:13]([NH:5][CH3:3])=[O:14]

Participants

5

Reactant 3

HCID 6329MethylamineHCID 8471TriethylamineHCID 27745412-Chloronicotinoyl chloride

Product 1

HCID 122869552-Chloro-N-methylnicotinamideYield 31.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
23 °C

Procedure

Methanamine (0.425 mL, 3.41 mmol) and triethylamine (0.792 mL, 5.68 mmol) were dissolved in CH3CN (14.2 mL) at 23° C. 2-Chloronicotinoyl chloride (500 mg, 2.84 mmol) was added and the reaction mixture was stirred at 23° C. for 16 h. The solvent was removed by rotary evaporation and the residue was partitioned between EtOAc (20 mL) and sat. aq. NaHCO3 (20 mL). The aqueous phase was extracted with EtOAc (3×20 mL). The combined organic phases were dried over MgSO4 and concentrated. Trituration of the resulting solid with 5% EtOAc-hexane provided the desired product as a white powder (153.2 mg, 31%). 1H NMR (CD3OD) δ 8.43 (dd, 1H, J=5.09, 2.03 Hz), 7.88 (dd, 1H, J=7.63, 2.03 Hz), 7.45 (dd, 1H, J=7.38, 4.83 Hz), 2.91 (s, 3H); MS(ESI+) m/z 171.1 (M+H)+.

Workup

  1. customThe solvent was removed by rotary evaporation
  2. customthe residue was partitioned between EtOAc (20 mL) and sat. aq. NaHCO3 (20 mL)
  3. extractionThe aqueous phase was extracted with EtOAc (3×20 mL)
  4. dry with materialThe combined organic phases were dried over MgSO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-de6be18994c24b7dbd2305fa1e3f484a
Source dataset
uspto-grants-2009_06
Patent number
US07547782B2

Reaction notes

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