Tetrabutylammonium Fluoride → 3-(4-((3-Chloro-2-fluorophenyl)ethynyl)-3-methoxyphenyl)-1-(2,6-dichlorophenyl)-1H-1,2,4-triazol-5(4H)-one

HRID 59488Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[C:13](=[O:14])[NH:12][C:11]([C:15]2[CH:20]=[CH:19][C:18](I)=[C:17]([O:22][CH3:23])[CH:16]=2)=[N:10]1.[Cl:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([C:31]#[CH:32])[C:26]=1[F:33].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>CS(C)=O.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>[Cl:24][C:25]1[C:26]([F:33])=[C:27]([C:31]#[C:32][C:18]2[CH:19]=[CH:20][C:15]([C:11]3[NH:12][C:13](=[O:14])[N:9]([C:3]4[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][C:4]=4[Cl:8])[N:10]=3)=[CH:16][C:17]=2[O:22][CH3:23])[CH:28]=[CH:29][CH:30]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 1-(2,6-dichlorophenyl)-3-(4-iodo-3-methoxyphenyl)-1H-1,2,4-triazol-5(4H)-one (Intermediate-45, 0.070 g, 0.15 mmol) in DMSO (3.0 mL) was added 1-chloro-3-ethynyl-2-fluorobenzene (Intermediate-24, 0.035 g, 0.22 mmol), TBAF (0.080 g, 0.30 mmol) and bis(triphenylphosphine)palladium(II) chloride (0.020 g, 0.022 mmol). The reaction mass was stirred at 80° C. for 5-6 h. The reaction mass was quenched in water and extracted with DCM and concentrated. The obtained product was purified with column chromatography on silica gel eluting with 2.0% EA:DCM to afford 0.020 g of the desired product. 1H NMR (300 MHz, DMSO d6): δ 3.92 (s, 3H), 7.29 (t, J=8.4 Hz, 1H), 7.48-7.72 (m, 8H), 12-13 (br s, 1H); MS (m/z): 488.00 (M+).

Workup

customThe reaction mass was quenched in water
extractionextracted with DCM
concentrationconcentrated
customThe obtained product was purified with column chromatography on silica gel eluting with 2.0% EA

Sources & evidence

ORD record: ord-7df6c3dd89a447298c83921661e8497f
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09439890B2

Reaction notes

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