Chlorosuccinimide → 2,3-Dichloro-N-methyl-4-pyridinecarboxamide

HRID 1355526Notes

Reaction equation

HRID 1355526 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([NH:7][CH3:8])=[O:6].[Li+].CC([N-]C(C)C)C.C1C(=O)N([Cl:27])C(=O)C1>C1COCC1>[Cl:1][C:2]1[C:3]([Cl:27])=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([NH:7][CH3:8])=[O:6]

Participants

5

Reactant 3

HCID 31398ChlorosuccinimideHCID 2724682Lithium diisopropylamideHCID 151158492-chloro-N-methylisonicotinamide

Product 1

HCID 185069202,3-Dichloro-N-methyl-4-pyridinecarboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

2-Chloro-N-methyl-isonicotinamide (12-2, 1.19 g, 6.98 mmol) was dissolved in 2 mL anhydrous THF and the solutin was cooled to −78° C. LDA (2M, 7.33 mL, 14.7 mmol) was added dropwise and the reaction turns orange. After 15 min NCS (1.02 g, 7.67 mmol) was added and the reaction was allowed to warm to RT. After 1 h at RT HPLC shows ˜3:1 starting material/product. The reaction was quenched with water, extracted 3× w/EtOAc, and the organic phases were dried over Na2SO4, filtered, and concentrated. The residue was purified by preparative reverse phase HPLC to afford the pure titled compound. 1H NMR (CDCl3) δ 8.36 (d, 1H, J=4.8 Hz), 7.41 (d, 1H, J=4.8 Hz), 6.10 (bs, 1H), 3.05 (d, 3H, J=4.9 Hz).

Workup

  1. temperatureto warm to RT
  2. customThe reaction was quenched with water
  3. extractionextracted 3× w/EtOAc
  4. dry with materialthe organic phases were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-69a24a0cb32a48df97ede8b52e5b6867
Source dataset
uspto-grants-2003_07
Patent number
US06586424B2

Reaction notes

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