Sodium Hydroxide → 6-bromo-N-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methyl)-1-isopropyl-1H-indazole-4-carboxamide

HRID 1854113Notes

Reaction equation

HRID 1854113 reaction equation
[OH-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]([C:16]([O:18]C)=O)[C:7]2[CH:8]=[N:9][N:10]([CH:13]([CH3:15])[CH3:14])[C:11]=2[CH:12]=1.[NH2:20][CH2:21][C:22]1[C:23](=[O:30])[NH:24][C:25]([CH3:29])=[CH:26][C:27]=1[CH3:28].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CCO.CS(C)=O>[Br:3][C:4]1[CH:5]=[C:6]([C:16]([NH:20][CH2:21][C:22]2[C:23](=[O:30])[NH:24][C:25]([CH3:29])=[CH:26][C:27]=2[CH3:28])=[O:18])[C:7]2[CH:8]=[N:9][N:10]([CH:13]([CH3:14])[CH3:15])[C:11]=2[CH:12]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 2724699PyBOPHCID 70638443-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-oneHCID 67464993Methyl 6-bromo-1-isopropyl-1H-indazole-4-carboxylate

Product 1

HCID 545964906-bromo-N-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methyl)-1-isopropyl-1H-indazole-4-carboxamideYield 43.2%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 702EthanolSolvent2×

Conditions

Temperature
60 °C

Procedure

Aqueous NaOH (1.5 equiv in 1 mL water) was added to a solution of methyl 6-bromo-1-isopropyl-1H-indazole-4-carboxylate (1.5 g, 4.8 mmol) in EtOH (20 mL) and stirred at 60° C. for 1 h. After completion of the reaction, ethanol was removed under reduced pressure and acidified using 1N HCl solution. Extraction was carried out using ethyl acetate and the combined organic layers washed with water, brine and dried over anhydrous Na2SO4 before filtration and concentrated under reduced pressure. The crude acid (1.26 g, 4.45 mmol) was then dissolved in DMSO (5 mL) and 3-(aminomethyl)-4,6-dimethylpyridin-2(1H)-one (1.35 g, 8.90 mmol) was added. The reaction mixture was stirred at room temperature for 15 min before PYBOP (3.47 g, 6.67 mmol) was added to it and stirring continued overnight. After completion of the reaction, the mixture was poured into ice and the resulting precipitate filtered and washed with acetonitrile followed by ether to provide 6-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-1H-indazole-4-carboxamide (0.8 g, 43.2%).

Workup

  1. customwas removed under reduced pressure
  2. extractionExtraction
  3. washthe combined organic layers washed with water, brine
  4. dry with materialdried over anhydrous Na2SO4 before filtration
  5. concentrationconcentrated under reduced pressure
  6. additionwas added to it
  7. stirringstirring continued overnight
  8. customAfter completion of the reaction
  9. additionthe mixture was poured into ice
  10. filtrationthe resulting precipitate filtered
  11. washwashed with acetonitrile

Sources & evidence

ORD record
ord-0c21516d0047443ca5bc073c46d203e7
Source dataset
uspto-grants-2015_02
Patent number
US08962620B2

Reaction notes

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