Acetonitrile → 6-Chloro-2-[(2-methoxy-ethyl)-methyl-amino]-nicotinamide

HRID 1255665Notes

Reaction equation

HRID 1255665 reaction equation
Cl[C:2]1[N:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].BrC1C=CC(O)=C[C:14]=1[CH:20]1OC[CH2:22][O:21]1.[OH-].[Na+].[C:27](#[N:29])C>>[Cl:11][C:9]1[CH:8]=[CH:7][C:3]([C:4]([NH2:6])=[O:5])=[C:2]([N:29]([CH2:14][CH2:20][O:21][CH3:22])[CH3:27])[N:10]=1

Participants

5

Reactant 4

HCID 6342AcetonitrileHCID 14798Sodium HydroxideHCID 221427782,6-Dichloropyridine-3-carboxamideHCID 579687074-Bromo-3-(1,3-dioxolan-2-yl)phenol

Product 1

HCID 579689526-Chloro-2-[(2-methoxy-ethyl)-methyl-amino]-nicotinamideYield 91%

Conditions

Temperature
60 °C

Procedure

To a solution of 2,6-dichloro-nicotinamide (1) (10 g, 52.9 mmol) in acetonitrile (anhydrous, 200 mL) was added (2-methoxy-ethyl)-methyl-amine (2) (18.8 g, 212 mmol). The reaction was heated at 60° C. for 1.5 hours. 5% NaOH solution (1000 mL) was slowly added. The solution was then extracted with EtOAc (3×250 mL). The combined organic layer was dried over MgSO4, filtered, and evaporated in vacuo. Purification was accomplished by silica gel chromatography, eluting with 5%-30% EtOAc/hexanes gradient, to afford 11.66 g (91% yield) of the title compound. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.07 (d, J=8.6 Hz, 1H), 7.76 (br. s., 1H), 6.93 (d, J=8.2 Hz, 1H), 5.66 (br. s., 1H), 3.66-3.51 (m, 4H), 3.32 (s, 3H), 2.93 (s, 3H).

Workup

  1. extractionThe solution was then extracted with EtOAc (3×250 mL)
  2. dry with materialThe combined organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customPurification
  6. washeluting with 5%-30% EtOAc/hexanes gradient

Sources & evidence

ORD record
ord-2913a02686a04358b7c31864f6ff900f
Source dataset
uspto-grants-2013_06
Patent number
US08461135B2

Reaction notes

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