Dichloromethane → 7-(4-chlorophenyl)-8-(4-methoxyphenyl)-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

HRID 2101302

Reaction equation

HRID 2101302 reaction equation
Br[C:2]1[C:3]2[N:4]([C:15](=[O:30])[N:16]([CH2:18][C:19]3[C:20](C)=[N:21][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:23][CH:24]=3)[N:17]=2)[CH:5]=[CH:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=1.[CH3:31][O:32][C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1.C(Cl)Cl.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CCOC(C)=O.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1COCC1>[Cl:14][C:11]1[CH:12]=[CH:13][C:8]([C:7]2[CH:6]=[CH:5][N:4]3[C:15](=[O:30])[N:16]([CH2:18][C:19]4[CH:20]=[N:21][C:22]([C:25]([F:26])([F:27])[F:28])=[CH:23][CH:24]=4)[N:17]=[C:3]3[C:2]=2[C:36]2[CH:37]=[CH:38][C:33]([O:32][CH3:31])=[CH:34][CH:35]=2)=[CH:9][CH:10]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 201262(4-Methoxyphenyl)boronic acidHCID 577994058-bromo-7-(4-chlorophenyl)-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

Product 1

HCID 160049417-(4-chlorophenyl)-8-(4-methoxyphenyl)-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-oneYield 65.6%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

Into a 5 dram vial at room temperature were placed a magnetic stirbar, 8-bromo-7-(4-chlorophenyl)-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (100 mg, 0.20 mmol), 4-methoxyphenylboronic acid (94 mg, 0.60 mmol), Pd(dppf)Cl2.CH2Cl2 (17 mg, 0.02 mmol), powdered anhydrous K3PO4 (133 mg, 0.60 mmol), and dry THF (3 mL). The vial was flushed with argon and then capped tightly. The vial was heated to 90° C. for 6 h while stirring. Analysis by HPLC/MS indicated that starting material was absent and one major new product had formed. The reaction mixture was diluted with EtOAc (20 mL) and water (20 mL). The organic layer was separated, and the aqueous layer was extracted with EtOAc. The combined organic extract was dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified by automated silica gel chromatography (eluted with EtOAc/hexanes) to obtain the title compound (67 mg) as an oil. HPLC/MS: retention time=4.0 min, [M+H]+=511.

Workup

  1. customvial at room temperature
  2. customThe vial was flushed with argon
  3. customcapped tightly
  4. customone major new product had formed
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with EtOAc
  7. extractionThe combined organic extract
  8. dry with materialwas dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe crude product was purified by automated silica gel chromatography (eluted with EtOAc/hexanes)

Sources & evidence

ORD record
ord-834ef4fe6f8e4bc2b8d166689974bb5c
Source dataset
uspto-grants-2009_08
Patent number
US07572808B2

Linked notes

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