Sodium Carbonate → HCID 57799422, compound

HRID 2101287Notes

Reaction equation

HRID 2101287 reaction equation
Br[C:2]1[C:3]2[N:4]([C:9](=[O:24])[N:10]([CH2:12][C:13]3[C:14]([CH3:23])=[N:15][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:17][CH:18]=3)[N:11]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].CC1(C)C(C)(C)OB([C:33]2[CH:38]=[CH:37][N:36]=[CH:35][CH:34]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.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:8][C:7]1[CH:6]=[CH:5][N:4]2[C:9](=[O:24])[N:10]([CH2:12][C:13]3[C:14]([CH3:23])=[N:15][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:17][CH:18]=3)[N:11]=[C:3]2[C:2]=1[C:33]1[CH:38]=[CH:37][N:36]=[CH:35][CH:34]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27346484-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 577994118-bromo-7-chloro-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one2×

Product 1

HCID 57799422HCID 57799422, compoundYield 63.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of 8-bromo-7-chloro-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (506 mg, 1.2 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (984 mg, 4.8 mmol), and 2.0 M aqueous sodium carbonate (2.6 mL) in toluene (10 mL) was added (Ph3P)4Pd (208 mg, 0.18 mmol) in one portion, and the resulting yellow mixture was vigorously stirred under argon at 100° C. Analysis by HPLC/MS after 2.5 h indicated about 70% of starting 8-bromo-7-chloro-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one remained. Additional (Ph3P)4Pd (60 mg, 0.05 mmol) was added. After stirring for 3 h more, the same amount of catalyst was again added, and the reaction mixture was stirred at 100° C. under argon for 5 h more. After cooling to room temperature, the reaction mixture was diluted with water and extracted with EtOAc (40 mL×3). The combined EtOAc extracts were washed with water, then saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated under reduced pressure to afford crude product, which was purified using a silica gel cartridge (80 g) eluted with a gradient of EtOAc (0-100%) in hexanes to afford the title compound as a white foam (320 mg, 62%). HPLC/MS: retention time=2.14 min, [M+H]+=420.1.

Workup

  1. stirringAfter stirring for 3 h more
  2. additionthe same amount of catalyst was again added
  3. stirringthe reaction mixture was stirred at 100° C. under argon for 5 h more
  4. temperatureAfter cooling to room temperature
  5. extractionextracted with EtOAc (40 mL×3)
  6. washThe combined EtOAc extracts were washed with water
  7. dry with materialsaturated aqueous NaCl, dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto afford crude product, which
  11. customwas purified
  12. washeluted with a gradient of EtOAc (0-100%) in hexanes

Sources & evidence

ORD record
ord-afd9dff1f74b4810a36a214420445ae1
Source dataset
uspto-grants-2009_08
Patent number
US07572808B2

Reaction notes

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