Cesium carbonate → 2-[6-(5-Bromo-1-methyl-2-oxo-1,2-dihydro-pyridin-3-ylamino)-pyridin-3-yl]-2-methyl-propionic acid methyl ester

HRID 2069722Notes

Reaction equation

HRID 2069722 reaction equation
[CH3:1][O:2][C:3](=[O:14])[C:4]([C:7]1[CH:8]=[N:9][C:10]([NH2:13])=[CH:11][CH:12]=1)([CH3:6])[CH3:5].Br[C:16]1[C:17](=[O:24])[N:18]([CH3:23])[CH:19]=[C:20]([Br:22])[CH:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[CH3:1][O:2][C:3](=[O:14])[C:4]([C:7]1[CH:8]=[N:9][C:10]([NH:13][C:16]2[C:17](=[O:24])[N:18]([CH3:23])[CH:19]=[C:20]([Br:22])[CH:21]=2)=[CH:11][CH:12]=1)([CH3:6])[CH3:5]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 36143503,5-Dibromo-1-methylpyridin-2(1H)-oneHCID 21998700Methyl 2-(6-aminopyridin-3-yl)-2-methylpropanoate

Product 1

HCID 594738062-[6-(5-Bromo-1-methyl-2-oxo-1,2-dihydro-pyridin-3-ylamino)-pyridin-3-yl]-2-methyl-propionic acid methyl esterYield 62%

Reagents, catalysts & solvents 1

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalyst

Procedure

2-(6-Amino-pyridin-3-yl)-2-methyl-propionic acid methyl ester (1.5 g, 7.7 mmol), 3,5- dibromo-1-methyl-1H-pyridin-2-one (2.05 g, 7.7 mmol), cesium carbonate (7.53 g, 23.1 mmol), bis(dibenzylideneacetone)palladium (353 mg, 0.385 mmol), and Xantphos (446 mg, 0.77 mmol) were added to a round bottom flask and the flask was purged with nitrogen. Degassed dioxane (50 ml) was added through a syringe. The reaction mixture was heated at 100 degrees centigrade overnight. The reaction mixture was filtered through celite and concentrated. The crude product was purified by flash chromatography using a gradient of 0% to 50% ethyl acetate in hexanes to give 1.8 g (62%) of 2-[6-(5-bromo-1-methyl-2-oxo-1,2-dihydro-pyridin-3-ylamino)-pyridin-3-yl]-2-methyl-propionic acid methyl ester.

Workup

  1. customthe flask was purged with nitrogen
  2. additionDegassed dioxane (50 ml) was added through a syringe
  3. temperatureThe reaction mixture was heated at 100 degrees centigrade overnight
  4. filtrationThe reaction mixture was filtered through celite
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-e0e5b0e074e64630a01c2adc69562969
Source dataset
uspto-grants-2012_10
Patent number
US08299077B2

Reaction notes

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