Methylamine → 2-chloro-N-methylisonicotinamide

HRID 1355458Notes

Reaction equation

HRID 1355458 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=1)[C:5](O)=[O:6].C(Cl)(=O)C(Cl)=O.[CH3:17][NH2:18]>C1COCC1.CN(C=O)C.CCO>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=1)[C:5]([NH:18][CH3:17])=[O:6]

Participants

7

Reactant 3

HCID 6329MethylamineHCID 65578Oxalyl chlorideHCID 2369852-Chloroisonicotinic acid

Product 1

HCID 151158492-chloro-N-methylisonicotinamide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

2-Chloro-isonicotinic acid (12-1, 5.15 g, 32.7 mmol) was stirred in 65 mL anhydrous THF under N2. The reaction (not homogeneous) was cooled to 0° C. and oxalyl chloride (2.85 mL, 32.7 mmol) was added, followed by addition of 1 drop anh DMF. Slight bubbling occurs. The reaction was allowed to warm to RT. After 4 h reaction is homogeneous and after a total of 5 h the reaction was quickly added by pipet to a solution of methylamine (7.11 g, 228 mmol) in EtOH (20 mL). The resulting solution was concentrated in vacuo and diluted with sat NaHCO3 (aq). The solution was extracted 3× with EtOAc and the organic extracts were dried over Na2SO4, filtered ands concentrated to provide the titled compound. 1H NMR (CDCl3) δ8.50 (d, 1H, J=5.1 Hz), 7.66 (s, 1H), 7.53 (d, 1H, J=5.1 Hz), 6.36 (bs, 1H), 3.04 (d, 2H, J=5.0 Hz).

Workup

  1. customThe reaction (not homogeneous)
  2. customSlight bubbling
  3. temperatureto warm to RT
  4. customAfter 4 h reaction
  5. concentrationThe resulting solution was concentrated in vacuo
  6. additiondiluted with sat NaHCO3 (aq)
  7. extractionThe solution was extracted 3× with EtOAc
  8. dry with materialthe organic extracts were dried over Na2SO4
  9. filtrationfiltered ands
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-9e6992f9ba364fac8fe3f0b6b2f31840
Source dataset
uspto-grants-2003_07
Patent number
US06586423B2

Reaction notes

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