Sodium Carbonate → HCID 16004906, compound

HRID 2101289Notes

Reaction equation

HRID 2101289 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]2[C:8](=[O:23])[N:9]([CH2:11][C:12]3[C:13]([CH3:22])=[N:14][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:16][CH:17]=3)[N:10]=[C:4]2[C:3]=1[C:24]1[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=1.[C:30]([C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1)#[N:31].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.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>[CH3:22][C:13]1[C:12]([CH2:11][N:9]2[C:8](=[O:23])[N:5]3[CH:6]=[CH:7][C:2]([C:35]4[CH:36]=[CH:37][C:32]([C:30]#[N:31])=[CH:33][CH:34]=4)=[C:3]([C:24]4[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=4)[C:4]3=[N:10]2)=[CH:17][CH:16]=[C:15]([C:18]([F:21])([F:20])[F:19])[N:14]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343264-Cyanophenylboronic acidHCID 577994227-chloro-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one2×

Product 1

HCID 16004906HCID 16004906, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of 7-chloro-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (135 mg, 0.32 mmol), 4-cyanophenylboronic acid (189 mg, 1.29 mmol), and 2.0 M aqueous sodium carbonate (0.70 mL) in toluene (2.5 mL) was added (Ph3P)4Pd (55 mg, 0.048 mmol) in one portion, and the resulting yellow mixture was vigorously stirred under argon at 100° C. for 1.5 h. Analysis by HPLC/MS indicated about 30% of the starting 7-chloro-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one remained. Additional catalyst (35 mg, 0.030 mmol) was added. The reaction mixture was stirred at 100° C. for 2 h more. After cooling to room temperature, the reaction mixture was partitioned between EtOAc and water. The EtOAc layer was washed with water, then saturated aqueous NaCl twice, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified using a silica gel cartridge (40 g) eluted with a gradient of EtOAc (0-80%) in hexanes to afford the desired product, which was dissolved in acetonitrile, frozen and lyophilized to afford 80 mg of the title compound as a light yellow powder. HPLC/MS: retention time=2.39 min, [M+H]+=487.2.

Workup

  1. stirringThe reaction mixture was stirred at 100° C. for 2 h more
  2. temperatureAfter cooling to room temperature
  3. customthe reaction mixture was partitioned between EtOAc and water
  4. washThe EtOAc layer was washed with water
  5. dry with materialsaturated aqueous NaCl twice, dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified
  9. washeluted with a gradient of EtOAc (0-80%) in hexanes

Sources & evidence

ORD record
ord-ada187840ebf4015b3b125e1856e5afd
Source dataset
uspto-grants-2009_08
Patent number
US07572808B2

Reaction notes

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