Tetrabutylammonium Fluoride → 5-(2-Chloro-6-fluorophenyl)-2-(4-{[5-(trifluoromethyl)pyridin-2-yl]ethynyl}phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 59430

Reaction equation

HRID 59430 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[NH:10][C:11](=[O:22])[N:12]([C:14]2[CH:19]=[CH:18][C:17]([C:20]#[CH:21])=[CH:16][CH:15]=2)[N:13]=1.Br[C:24]1[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][N:25]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CS(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[NH:10][C:11](=[O:22])[N:12]([C:14]2[CH:19]=[CH:18][C:17]([C:20]#[C:21][C:24]3[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][N:25]=3)=[CH:16][CH:15]=2)[N:13]=1

Participants

6

Reactant 3

HCID 2724141Tetrabutylammonium FluorideHCID 27364342-Bromo-5-(trifluoromethyl)pyridineHCID 1366448585-(2-chloro-6-fluorophenyl)-2-(4-ethynylphenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one

Product 1

HCID 1364924235-(2-Chloro-6-fluorophenyl)-2-(4-{[5-(trifluoromethyl)pyridin-2-yl]ethynyl}phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-oneYield 20.5%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

The title compound was prepared according to the procedure described in Example-3 using 5-(2-chloro-6-fluorophenyl)-2-(4-ethynylphenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one (Intermediate-2, 0.100 g, 0.319 mmol), 2-bromo-5-(trifluoromethyl)pyridine (0.108 g, 0.479 mmol), TBAF (0.201 g, 0.638 mmol), bis(triphenylphosphine)palladium(II) chloride (0.020 g, 0.028 mmol) and DMSO (3.0 mL). The obtained product was purified with column chromatography on silica gel eluting with 1.0% MeOH:DCM to afford 0.030 g of the desired product. 1H NMR (300 MHz, DMSO d6): δ 7.51 (t, J=8.7 Hz, 1H), 7.59 (d, J=7.8 Hz, 1H), 7.70 (t, J=6.3 Hz, 1H), 7.79 (d, J=8.7 Hz, 2H), 7.89 (d, J=8.1 Hz, 1H), 8.06 (d, J=8.4 Hz, 2H), 8.29 (d, J=7.8 Hz, 11-0, 9.00 (s, 1H), 12.75 (br s, 1H). MS (m/z): 459.37 (M+).

Workup

  1. customThe title compound was prepared
  2. customThe obtained product was purified with column chromatography on silica gel eluting with 1.0% MeOH

Sources & evidence

ORD record
ord-b8bc67b7ab63467e97b4802ebc0a7f49
Source dataset
uspto-grants-2016_09
Patent number
US09439890B2

Linked notes

Loading…