N-bromobutanimide → 6-(4-bromo-5-methoxy-1H-pyrazol-1-yl)-N-(3-methoxypropyl)nicotinamide

HRID 526416Notes

Reaction equation

HRID 526416 reaction equation
[CH3:1][O:2][C:3]1[N:7]([C:8]2[CH:13]=[CH:12][C:11]([C:14](=[O:21])[NH:15][CH2:16][CH2:17][CH2:18][O:19][CH3:20])=[CH:10][N:9]=2)[N:6]=[CH:5][C:4]=1C(O)=O.C1C(=O)N([Br:32])C(=O)C1.C(=O)(O)[O-].[Na+]>CN(C=O)C.O>[Br:32][C:4]1[CH:5]=[N:6][N:7]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([NH:15][CH2:16][CH2:17][CH2:18][O:19][CH3:20])=[O:21])=[CH:10][N:9]=2)[C:3]=1[O:2][CH3:1]

Participants

6

Reactant 3

HCID 67184N-bromobutanimideHCID 516892Sodium BicarbonateHCID 1176011115-methoxy-1-(5-((3-methoxypropyl)carbamoyl)pyridin-2-yl)-1H-pyrazole-4-carboxylic acid

Product 1

HCID 1176012696-(4-bromo-5-methoxy-1H-pyrazol-1-yl)-N-(3-methoxypropyl)nicotinamideYield 97.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Combined 5-methoxy-1-(5-((3-methoxypropyl)carbamoyl)pyridin-2-yl)-1H-pyrazole-4-carboxylic acid (2.19 g, 6.55 mmol), NBS (1.749 g, 9.83 mmol), and sodium bicarbonate (1.651 g, 19.65 mmol) in DMF (20 mL) and stirred at 20° C. for 1 h. The reaction was diluted with water (100 mL) and extracted with EtOAc (100 mL, then 2×50 mL). The combined organics were washed with brine, dried over magnesium sulfate and concentrated in vacuo to give a residue which was purified on a 120 g silica gel column eluted with 10 to 100% EtOAc in hexanes to give the title compound (2.348 g, 97% yield) as a white solid. MS m/z 369, 371 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.78 (quin, J=6.6 Hz, 2H) 3.25 (s, 3H) 3.30-3.37 (m, 2H) 3.40 (t, J=6.3 Hz, 2H) 4.05 (s, 3H) 7.79 (dd, J=8.6, 0.5 Hz, 1H) 7.85 (s, 1H) 8.38 (dd, J=8.6, 2.3 Hz, 1H) 8.74 (t, J=5.6 Hz, 1H) 8.96 (dd, J=2.4, 0.6 Hz, 1H).

Workup

  1. extractionextracted with EtOAc (100 mL
  2. washThe combined organics were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customto give a residue which
  6. customwas purified on a 120 g silica gel column
  7. washeluted with 10 to 100% EtOAc in hexanes

Sources & evidence

ORD record
ord-d215c7c7e03b4ea199be8e2d36737b19
Source dataset
uspto-grants-2016_05
Patent number
US09345713B2

Reaction notes

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