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

HRID 2101305

Reaction equation

HRID 2101305 reaction equation
Br[C:2]1[C:3]2[N:4]([C:15](=[O:29])[N:16]([CH2:18][C:19]3[CH:20]=[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.[C:30]([C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1)(=[O:32])[CH3:31].C(Cl)Cl.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1COCC1.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]>[C:30]([C:33]1[CH:38]=[CH:37][C:36]([C:2]2[C:3]3[N:4]([C:15](=[O:29])[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]=3)[CH:5]=[CH:6][C:7]=2[C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=2)=[CH:35][CH:34]=1)(=[O:32])[CH3:31]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 37021224-Acetylphenylboronic acidHCID 577994658-bromo-7-(4-chlorophenyl)-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

Product 1

HCID 160051638-(4-acetylphenyl)-7-(4-chlorophenyl)-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

To a stirring solution of 8-bromo-7-(4-chlorophenyl)-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (170 mg, 0.35 mmol) in THF (5 mL) at room temperature under argon was added 4-acetylphenylboronic acid (173 mg, 1.05 mmol), Pd(dppf)Cl2.CH2Cl2 (32.2 mg, 0.035 mmol), and K3PO4 (224 mg, 1.05 mmol). The resulting suspension was purged of oxygen by bubbling with argon for 15 min, sealed in a vial under argon, heated at 90° C. for 12 h, and then cooled to room temperature. The reaction mixture was diluted with EtOAc and washed once with brine. The organic layer was dried (MgSO4), filtered, and concentrated under reduced pressure. The crude product was purified by automated silica gel chromatography (eluted with EtOAc/hexanes). Pooling of the desired fractions, washing with saturated aq. NaHCO3 solution to eliminate any possible boronic acid contaminant, drying the organic phase (MgSO4), filtering and evaporation provided the title compound as a yellow solid, after recrystallization from EtOAc/hexanes, to obtain 110 mg, 60%. HPLC/MS: retention time=3.20 min, [M+H]+=523. 1H NMR (CDCl3): δ 8.77 (s, 1H), 7.88 (m, 4H), 7.66 (d, J=8.2 Hz, 1H), 7.35 (d, J=8.3 Hz, 2H), 7.23 (d, J=8.3 Hz, 2H), 7.04 (d, J=8.2 Hz, 2H), 6.66 (d, J=7.2 Hz, 2H), 5.25 (s, 2H), 2.60 (s, 3H).

Workup

  1. customThe resulting suspension was purged of oxygen
  2. customby bubbling with argon for 15 min
  3. customsealed in a vial under argon
  4. temperaturecooled to room temperature
  5. additionThe reaction mixture was diluted with EtOAc
  6. washwashed once with brine
  7. dry with materialThe organic layer was dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product was purified by automated silica gel chromatography (eluted with EtOAc/hexanes)
  11. washPooling of the desired fractions, washing with saturated aq. NaHCO3 solution
  12. dry with materialdrying the organic phase (MgSO4)
  13. filtrationfiltering
  14. customevaporation

Sources & evidence

ORD record
ord-c06b8add89d94605b9a8a5db881f949d
Source dataset
uspto-grants-2009_08
Patent number
US07572808B2

Linked notes

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