3-Amino-5-bromo-1-methyl-1,2-dihydropyridin-2-one → N-[3-(5-Amino-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-2-methyl-phenyl]-4-tert-butyl-benzamide

HRID 1174560Notes

Reaction equation

HRID 1174560 reaction equation
[NH2:1][C:2]1[C:3](=[O:10])[N:4]([CH3:9])[CH:5]=[C:6](Br)[CH:7]=1.[C:11]([C:15]1[CH:39]=[CH:38][C:18]([C:19]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24](B3OC(C)(C)C(C)(C)O3)[C:23]=2[CH3:37])=[O:20])=[CH:17][CH:16]=1)([CH3:14])([CH3:13])[CH3:12]>COCCOC.C([O-])([O-])=O.[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:1][C:2]1[C:3](=[O:10])[N:4]([CH3:9])[CH:5]=[C:6]([C:24]2[C:23]([CH3:37])=[C:22]([NH:21][C:19](=[O:20])[C:18]3[CH:17]=[CH:16][C:15]([C:11]([CH3:12])([CH3:13])[CH3:14])=[CH:39][CH:38]=3)[CH:27]=[CH:26][CH:25]=2)[CH:7]=1

Participants

6

Reactant 2

HCID 529112683-Amino-5-bromo-1-methyl-1,2-dihydropyridin-2-oneHCID 587289934-(tert-Butyl)-N-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)benzamide

Product 1

HCID 59557875N-[3-(5-Amino-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-2-methyl-phenyl]-4-tert-butyl-benzamideYield 71.9%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
95 °C

Procedure

A 48-mL seal tube equipped with a magnetic stirring bar was charged with 3-amino-5-bromo-1-methyl-1H-pyridin-2-one (2) (0.10 g, 0.50 mmol), 4-tert-butyl-N-[2-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-benzamide (0.24 g, 0.70 mmol), and Pd(PPh3)4 (0.030 g, 0.025 mmol) in DME (10 mL) and 1N Na2CO3 (5 mL). After the mixture was degassed for 15 min., it was heated at 95° C. for 16 h. Then, the reaction mixture was cooled to room temperature and poured into H2O (10 mL). To this was added dichloromethane and the phases were separated. The aqueous layer was extracted with dichloromethane, and the combined organic layers were washed with H2O (5 mL) and brine (5 mL), dried (Na2SO4), and concentrated. The crude mixture was purified by column chromatography, gradient 0-10% MeOH in dichloromethane/ether (1/1), to afford 0.14 g (68%) of N-[3-(5-amino-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-2-methyl-phenyl]-4-tert-butyl-benzamide (3) as a solid.

Workup

  1. customA 48-mL seal tube
  2. customequipped with a magnetic stirring bar
  3. customAfter the mixture was degassed for 15 min.
  4. temperatureThen, the reaction mixture was cooled to room temperature
  5. additionpoured into H2O (10 mL)
  6. additionTo this was added dichloromethane
  7. customthe phases were separated
  8. extractionThe aqueous layer was extracted with dichloromethane
  9. washthe combined organic layers were washed with H2O (5 mL) and brine (5 mL)
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated
  12. customThe crude mixture was purified by column chromatography, gradient 0-10% MeOH in dichloromethane/ether (1/1)

Sources & evidence

ORD record
ord-ad6e162399e146c789b2e2b242c75553
Source dataset
uspto-grants-2010_11
Patent number
US07838523B2

Reaction notes

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