3,3-Dimethyl-1-butyne → N-(4-Chloro-2-fluoro-3-(4,5-dihydro-3-(4-(3,3-dimethylbut-1-ynyl)phenyl)-5-oxo-1,2,4-triazol-1-yl)benzyl)pivalamide

HRID 59518

반응식

HRID 59518 반응식
[Cl:1][C:2]1[CH:15]=[CH:14][C:5]([CH2:6][NH:7][C:8](=[O:13])[C:9]([CH3:12])([CH3:11])[CH3:10])=[C:4]([F:16])[C:3]=1[N:17]1[C:21](=[O:22])[NH:20][C:19]([C:23]2[CH:28]=[CH:27][C:26](I)=[CH:25][CH:24]=2)=[N:18]1.[CH3:30][C:31]([CH3:35])([CH3:34])[C:32]#[CH: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:1][C:2]1[CH:15]=[CH:14][C:5]([CH2:6][NH:7][C:8](=[O:13])[C:9]([CH3:12])([CH3:11])[CH3:10])=[C:4]([F:16])[C:3]=1[N:17]1[C:21](=[O:22])[NH:20][C:19]([C:23]2[CH:28]=[CH:27][C:26]([C:33]#[C:32][C:31]([CH3:35])([CH3:34])[CH3:30])=[CH:25][CH:24]=2)=[N:18]1

참가 물질

6

반응물 3

HCID 135123,3-Dimethyl-1-butyneHCID 2724141Tetrabutylammonium FluorideHCID 136492417N-(4-Chloro-2-fluoro-3-(4,5-dihydro-3-(4-iodophenyl)-5-oxo-1,2,4-triazol-1-yl)benzyl)pivalamide

생성물 1

HCID 136246111N-(4-Chloro-2-fluoro-3-(4,5-dihydro-3-(4-(3,3-dimethylbut-1-ynyl)phenyl)-5-oxo-1,2,4-triazol-1-yl)benzyl)pivalamide수율 48.5%

시약·촉매·용매 2

HCID 178418476HCID 178418476, 화합물촉매HCID 679Dimethyl Sulfoxide용매

반응 조건

온도
80 °C

실험 절차

To a solution of N-(4-chloro-2-fluoro-3-(4,5-dihydro-3-(4-iodophenyl)-5-oxo-1,2,4-triazol-1-yl)benzyl)pivalamide (Intermediate-68, 0.050 g, 0.094 mmol) in DMSO (3.0 mL), 3,3-dimethylbut-1-yne (0.011 g, 0.142 mmol), TBAF (0.074 g, 0.283 mmol) and bis(triphenylphosphine)palladium(II) chloride (0.020 g, 0.022 mmol) were added and the reaction mass was stirred at 80° C. for 5-6 h. After completion of the reaction, the reaction mass was quenched with water and extracted with DCM and concentrated. The obtained crude product was purified with column chromatography on silica gel column and 2.0% EA:DCM as mobile phase to afford 0.022 g of the desired title product. 1H NMR (400 MHz, DMSO d6): δ 1.09 (s, 9H), 1.25 (s, 9H), 4.31 (br s, 2H), 7.35-7.51 (m, 4H), 7.80 (d, J=8.3 Hz, 2H), 8.18-8.20 (m, 1H); MS (m/z): 481.14 (M−H)−.

후처리

  1. customAfter completion of the reaction
  2. customthe reaction mass was quenched with water
  3. extractionextracted with DCM
  4. concentrationconcentrated
  5. customThe obtained crude product
  6. customwas purified with column chromatography on silica gel column and 2.0% EA

출처 및 근거

ORD 기록
ord-a15491252e9647098a0d7bf035a92901
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09439890B2

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