Triethylamine → 5-bromo-N,2-dimethoxy-N-methylnicotinamide

HRID 1776890Notes

Reaction equation

HRID 1776890 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][C:5]([O:11][CH3:12])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[CH3:34][NH:35][O:36][CH3:37].Cl.CCN(CC)CC>CN(C=O)C>[Br:1][C:2]1[CH:3]=[N:4][C:5]([O:11][CH3:12])=[C:6]([CH:10]=1)[C:7]([N:35]([O:36][CH3:37])[CH3:34])=[O:9]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 143717285-Bromo-2-methoxypyridine-3-carboxylic acid

Product 1

HCID 594686735-bromo-N,2-dimethoxy-N-methylnicotinamideYield 92.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-bromo-2-methoxynicotinic acid (15.0 g, 64.65 mmol) in anhydrous DMF (150 mL), HOBT (9.0 g, 66.61 mmol) and EDCI (25.0 g, 130.41 mmol) were added. The reaction mixture was stirred at room temperature for 2 hour. And then MeNHOMe.HCl (20.0 g, 205.04 mmol) and Et3N (60 mL, 415.06 mmol) was added to the mixture. The mixture was stirred at 20° C. overnight. The reaction mixture was concentrated in vacuo. Then H2O was added, and extracted with EtOAc. The combined organic phases were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified using column chromatography (eluted with petroleum ether:EtOAc=2:1) to provide 5-bromo-N,2-dimethoxy-N-methylnicotinamide (16.5 g, yield: 92%). 1H-NMR (CDCl3, 400 MHz) δ 8.23 (d, J=2.4 Hz, 1H), 7.68 (d, J=2.4 Hz, 1H), 3.95 (s, 3H), 3.53 (s, 3H), 3.33 (s, 3H). MS (M+H)+: 275/277.

Workup

  1. stirringThe mixture was stirred at 20° C. overnight
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. additionThen H2O was added
  4. extractionextracted with EtOAc
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified
  10. washcolumn chromatography (eluted with petroleum ether:EtOAc=2:1)

Sources & evidence

ORD record
ord-2f30f520e4c8478da499933d70703de0
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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