Potassium Carbonate → 8-(4-chlorophenyl)-2-(methoxymethyl)-7-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

HRID 2101353Notes

Reaction equation

HRID 2101353 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]2[C:8](=[O:14])[N:9]([CH2:11][O:12][CH3:13])[N:10]=[C:4]2[C:3]=1[C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=1.CC1(C)C(C)(C)OB([C:30]2[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=2)O1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.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:21][C:18]1[CH:19]=[CH:20][C:15]([C:3]2[C:4]3[N:5]([C:8](=[O:14])[N:9]([CH2:11][O:12][CH3:13])[N:10]=3)[CH:6]=[CH:7][C:2]=2[C:30]2[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=2)=[CH:16][CH:17]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27346484-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 577993697-bromo-8-(4-chlorophenyl)-2-(methoxymethyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

Product 1

HCID 577994188-(4-chlorophenyl)-2-(methoxymethyl)-7-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-oneYield 80.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
20 °C

Procedure

To a degassed mixture of 7-bromo-8-(4-chlorophenyl)-2-(methoxymethyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (300 mg, 0.81 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (332 mg, 1.62 mmol) and K2CO3 (280 mg, 2.0 mmol) in 1,4-dioxane (10 mL) and H2O (3.0 mL) under argon at 20° C. was added Pd(PPh3)4 (47 mg, 0.043 mmol). The reaction mixture was refluxed for 15 h under argon and then cooled to 20° C. The reaction mixture was diluted with H2O (10 mL) and extracted with EtOAc (3×20 mL). The combined organic extract was washed with saturated aqueous NaHCO3 solution (20 mL), then brine (20 mL), dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography eluting with a 0-60% gradient of EtOAc in hexanes to obtain the title compound as a yellow solid (241 mg, 0.65 mmol). MS: [M+H]+=367.2. 1H NMR (400 MHz, CDCl3) δ 3.45 (s, 3H), 5.32 (s, 2H), 6.59 (d, J=7.03 Hz, 1H), 7.04 (d, J=6.15 Hz, 2H), 7.18-7.23 (m, 2H), 7.26-7.30 (m, 2H), 7.85 (d, J=7.47 Hz, 1H), 8.53 (d, J=6.15 Hz, 2H).

Workup

  1. temperatureThe reaction mixture was refluxed for 15 h under argon
  2. extractionextracted with EtOAc (3×20 mL)
  3. extractionThe combined organic extract
  4. washwas washed with saturated aqueous NaHCO3 solution (20 mL)
  5. dry with materialbrine (20 mL), dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by silica gel column chromatography
  9. washeluting with a 0-60% gradient of EtOAc in hexanes

Sources & evidence

ORD record
ord-c65da459d3a7400aa3a106af1964bd50
Source dataset
uspto-grants-2009_08
Patent number
US07572808B2

Reaction notes

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