2-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-amine → N-(3-(5-Amino-6-methoxypyridin-3-yl)-2-methylphenyl)-4-tert-butylbenzamide

HRID 1174562Notes

Reaction equation

HRID 1174562 reaction equation
[CH3:1][O:2][C:3]1[C:8]([NH2:9])=[CH:7][C:6](B2OC(C)(C)C(C)(C)O2)=[CH:5][N:4]=1.Br[C:20]1[C:21]([CH3:39])=[C:22]([NH:26][C:27](=[O:38])[C:28]2[CH:33]=[CH:32][C:31]([C:34]([CH3:37])([CH3:36])[CH3:35])=[CH:30][CH:29]=2)[CH:23]=[CH:24][CH:25]=1>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>[NH2:9][C:8]1[CH:7]=[C:6]([C:20]2[C:21]([CH3:39])=[C:22]([NH:26][C:27](=[O:38])[C:28]3[CH:29]=[CH:30][C:31]([C:34]([CH3:35])([CH3:36])[CH3:37])=[CH:32][CH:33]=3)[CH:23]=[CH:24][CH:25]=2)[CH:5]=[N:4][C:3]=1[O:2][CH3:1]

Participants

6

Reactant 2

HCID 595579202-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-amineHCID 66886483N-(3-Bromo-2-methylphenyl)-4-(tert-butyl)benzamide

Product 1

HCID 59557884N-(3-(5-Amino-6-methoxypyridin-3-yl)-2-methylphenyl)-4-tert-butylbenzamideYield 64.2%

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 2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-amine (5) (1.0 g, 4.0 mmol), N-(3-bromo-2-methylphenyl)-4-tert-butylbenzamide (1.8 g, 5.0 mmol), and tetrakis(triphenylphosphine)palladium (0.20 g, 0.20 mmol) in DME (10 mL) and 1 N sodium carbonate (10 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 (20 mL) and the layers were separated. The aqueous phase was extracted with dichloromethane (3×10 mL), and the combined organic extracts 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, to afford 1.0 g (64%) of N-(3-(5-amino-6-methoxypyridin-3-yl)-2-methylphenyl)-4-tert-butylbenzamide (6) 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 (20 mL)
  7. customthe layers were separated
  8. extractionThe aqueous phase was extracted with dichloromethane (3×10 mL)
  9. washthe combined organic extracts 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

Sources & evidence

ORD record
ord-d8b8b1a520a84de7958ce8eb2839e300
Source dataset
uspto-grants-2010_11
Patent number
US07838523B2

Reaction notes

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