(6-Methoxypyridin-3-yl)boronic acid → HCID 58966946, compound

HRID 1948188Notes

Reaction equation

HRID 1948188 reaction equation
[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][N:7]2[CH:12]=[C:11](Br)[CH:10]=[CH:9][C:8]2=[O:14])=[C:4]([F:17])[CH:3]=1.[CH3:18][O:19][C:20]1[N:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1>O1CCOCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CCOC(C)=O.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>[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][N:7]2[CH:12]=[C:11]([C:23]3[CH:24]=[N:25][C:20]([O:19][CH3:18])=[CH:21][CH:22]=3)[CH:10]=[CH:9][C:8]2=[O:14])=[C:4]([F:17])[CH:3]=1

Participants

6

Reactant 2

HCID 2734368(6-Methoxypyridin-3-yl)boronic acidHCID 69349998HCID 69349998, compound

Product 1

HCID 58966946HCID 58966946, compoundYield 91%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 86614967HCID 86614967, compoundSolvent

Conditions

Temperature
80 °C

Procedure

According to Scheme 3 Method A: To a mixture of 1-(4-chloro-2-fluorobenzyl)-5-bromopyridin-2(1H)-one (1 eq, 1.00 mmol, 0.40 g) in dioxane/K3PO4 (2M, 10 mL), were added Pd(PPh3)4 (0.3 eq, 0.4 mmol, 0.4 g) and 6-methoxypyridin-3-ylboronic acid (1.5 eq, 2.00 mmol, 0.30 g) then the reaction mixture was heated at 80° C. for 17 hours. The mixture was diluted with AcOEt. The organic fraction washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel chromatography (AIT Flashsmart prepacked column 25 g SiO2, CH2Cl2/AcOEt 70/30) and by crystallization in pentane/Et2O to afford 1-(4-chloro-2-fluorobenzyl)-5-(6-methoxypyridin-3-yl)pyridin-2(1H)-one (0.91 mmol, 0.40 g, 91%) as a white solid.

Workup

  1. washThe organic fraction washed with brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was purified by silica gel chromatography (AIT Flashsmart prepacked column 25 g SiO2, CH2Cl2/AcOEt 70/30) and by crystallization in pentane/Et2O

Sources & evidence

ORD record
ord-2a54d9d2b0f0472d900e5dab17f2d086
Source dataset
uspto-grants-2013_03
Patent number
US08399493B2

Reaction notes

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