Tetrahydrofuran → 2-(4-(trifluoromethyl)benzyl)-7,8-dip-tolyl-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

HRID 2101278Notes

Reaction equation

HRID 2101278 reaction equation
[F:1][C:2]([F:29])([F:28])[C:3]1[CH:27]=[CH:26][C:6]([CH2:7][N:8]2[C:24](=[O:25])[N:11]3[CH:12]=[CH:13][C:14]([C:17]4[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=4)=[C:15](Cl)[C:10]3=[N:9]2)=[CH:5][CH:4]=1.C1COCC1.[CH3:35][C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=1.C([O-])([O-])=O.[K+].[K+]>CO>[F:1][C:2]([F:29])([F:28])[C:3]1[CH:27]=[CH:26][C:6]([CH2:7][N:8]2[C:24](=[O:25])[N:11]3[CH:12]=[CH:13][C:14]([C:17]4[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=4)=[C:15]([C:39]4[CH:40]=[CH:41][C:36]([CH3:35])=[CH:37][CH:38]=4)[C:10]3=[N:9]2)=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 79799Tolylboronic acidHCID 577994432-(4-(trifluoromethyl)benzyl)-8-chloro-7-p-tolyl-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

Product 1

HCID 160921052-(4-(trifluoromethyl)benzyl)-7,8-dip-tolyl-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-oneYield 61.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

To a stirring solution of 2-(4-(trifluoromethyl)benzyl)-8-chloro-7-p-tolyl-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (41.7 mg, 0.10 mmol) in a 1:1 mixture of THF and methanol (4 mL) at room temperature under argon was added 4-methylphenylboronic acid (40.8 g, 0.30 mmol), PXPd (16.2 g, 0.03 mmol), and K2CO3 (41 mg, 0.3 mmol). The resulting suspension was heated at 70° C. under argon for 10 min. Analysis by HPLC/MS indicated that starting material had been consumed. After cooling the reaction mixture to room temperature, water (25 mL) and EtOAc (25 mL) were added. The layers were separated. The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified by automated silica gel chromatography (eluted with ethyl acetate-hexanes) to obtain 29 mg of the title compound as a white lyophilate. HPLC/MS: retention time=4.36 min, [M+H]+=474. 1H NMR (CDCl3): δ 7.78 (d, J=7.5 Hz, 1H), 7.59 (d, J=7.1 Hz, 2H), 7.50 (d, J=7.1 Hz, 2H), 7.18 (d, J=8.0 Hz, 2H), 7.09-7.00 (m, 6H), 6.65 (d, J=7.5 Hz, 1H), 5.22 (s, 2H), 2.32 (s, 3H), 2.31 (s, 3H).

Workup

  1. customhad been consumed
  2. temperatureAfter cooling the reaction mixture to room temperature
  3. additionwater (25 mL) and EtOAc (25 mL) were added
  4. customThe layers were separated
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by automated silica gel chromatography (eluted with ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-d6a08dc7324249999b22babf644dc321
Source dataset
uspto-grants-2009_08
Patent number
US07572808B2

Reaction notes

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