Diisopropylethylamine → 3-(1-methyl-1H-pyrazol-4-yl)-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-quinoline

HRID 1890960노트

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HRID 1890960 반응식
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[N:9][C:10]3[C:15]([CH:16]=2)=[CH:14][C:13](OS(C(F)(F)F)(=O)=O)=[CH:12][CH:11]=3)[CH:4]=[N:3]1.C(N(C(C)C)CC)(C)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[CH3:76][C:77]1[CH:78]=[CH:79][C:80]2[N:81]([C:83]([SH:86])=[N:84][N:85]=2)[N:82]=1>CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[N:9][C:10]3[C:15]([CH:16]=2)=[CH:14][C:13]([S:86][C:83]2[N:81]4[N:82]=[C:77]([CH3:76])[CH:78]=[CH:79][C:80]4=[N:85][N:84]=2)=[CH:12][CH:11]=3)[CH:4]=[N:3]1

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 57742328trifluoro-methanesulfonic acid 3-(1-methyl-1H-pyrazol-4-yl)-quinolin-6-yl esterHCID 178423528HCID 178423528, 화합물

생성물 1

HCID 249009753-(1-methyl-1H-pyrazol-4-yl)-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-quinoline수율 79.5%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 6228Dimethylformamide용매

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온도
100 °C

실험 절차

A solution of trifluoro-methanesulfonic acid 3-(1-methyl-1H-pyrazol-4-yl)-quinolin-6-yl ester (15.9 g, 44.79 mmol), diisopropylethylamine (15.5 mL, 89.58 mmol) in DMF (150 mL) under nitrogen was degassed by bubbling with nitrogen for 30 min. Tris(dibenzylideneacetone)dipalladium (2.0 g, 2.24 mmol, Strem catalyst) and Xantphos (2.54 g, 4.48 mmol) were added together in one portion, followed by 6-methyl-[1,2,4]triazolo[4,3-b]pyridazine-3-thiol (7.44 g, 44.79 mmol) under a stream of nitrogen. The reaction mixture was stirred at 100° C. for 4 h. The reaction mixture was filtered while hot and the filtrate was cooled to precipitate. The solid was collected and washed with methanol to give an off-white solid, which was purified via column chromatography to get 13.3 g of 3-(1-methyl-1H-pyrazol-4-yl)-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl)-quinoline (79% yield).

후처리

  1. customby bubbling with nitrogen for 30 min
  2. filtrationThe reaction mixture was filtered while hot and the filtrate
  3. temperaturewas cooled
  4. customto precipitate
  5. customThe solid was collected
  6. washwashed with methanol
  7. customto give an off-white solid, which
  8. customwas purified via column chromatography

출처 및 근거

ORD 기록
ord-b488d63816be4f24a2f37fbd922df89d
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08507489B2

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