Sodium Hydroxide → 5-bromo-3-(cyclopentyl(ethyl)amino)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methylbenzamide

HRID 1616399Notes

Reaction equation

HRID 1616399 reaction equation
[OH-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]([N:15]([CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)[CH2:16][CH3:17])[C:7]([CH3:14])=[C:8]([CH:13]=1)[C:9]([O:11]C)=O.[NH2:23][CH2:24][C:25]1[C:26](=[O:33])[NH:27][C:28]([CH3:32])=[CH:29][C:30]=1[CH3:31].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>C(O)C.CS(C)=O>[Br:3][C:4]1[CH:5]=[C:6]([N:15]([CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)[CH2:16][CH3:17])[C:7]([CH3:14])=[C:8]([CH:13]=1)[C:9]([NH:23][CH2:24][C:25]1[C:26](=[O:33])[NH:27][C:28]([CH3:32])=[CH:29][C:30]=1[CH3:31])=[O:11]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 2724699PyBOPHCID 70638443-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-oneHCID 70872402Methyl 5-bromo-3-(cyclopentyl(ethyl)amino)-2-methylbenzoate

Product 1

HCID 665757665-bromo-3-(cyclopentyl(ethyl)amino)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methylbenzamideYield 42%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 702EthanolSolvent2×

Conditions

Temperature
60 °C

Procedure

Aqueous NaOH (0.126 g, 3.09 mmol) was added to a solution of methyl 5-bromo-3-(cyclopentyl(ethyl)amino)-2-methylbenzoate (0.7 g, 2.06 mmol) in ethanol (5 mL) and stirred at 60° C. for 1 h. After completion of the reaction, ethanol was removed under reduced pressure and the aqueous layer acidified using dilute HCl to pH 6 and citric acid to pH 4. The product was extracted using ethyl acetate. Combined organic layers were dried and concentrated to give the crude acid (0.5 g, 75%). The acid (0.5 g, 1.53 mmol) was then dissolved in DMSO (5 mL) and 3-(amino methyl)-4,6-dimethylpyridin-2(1H)-one (0.467 g, 3.07 mmol) was added to it. The reaction mixture was stirred at room temperature for 15 min before PYBOP (1.19 g, 2.30 mmol) was added to it and stirring was continued for overnight. After completion of the reaction, the reaction mixture was poured into ice, extracted with 10% MeOH/DCM. Combined organic layers were dried and concentrated, then the product was purified by column chromatography to afford 5-bromo-3-(cyclopentyl(ethyl)amino)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methylbenzamide (0.3 g, 42%).

Workup

  1. customwas removed under reduced pressure
  2. extractionThe product was extracted
  3. customCombined organic layers were dried
  4. concentrationconcentrated
  5. customto give the crude acid (0.5 g, 75%)
  6. additionwas added to it
  7. stirringstirring
  8. waitwas continued for overnight
  9. customAfter completion of the reaction
  10. additionthe reaction mixture was poured into ice
  11. extractionextracted with 10% MeOH/DCM
  12. customCombined organic layers were dried
  13. concentrationconcentrated
  14. customthe product was purified by column chromatography

Sources & evidence

ORD record
ord-a7293892615547f1a058fc3afe30accb
Source dataset
uspto-grants-2014_07
Patent number
US08765732B2

Reaction notes

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