Tetrabutylammonium Fluoride → 4-methoxy-3-[(5-methyl-1-phenyl-1H-pyrazol-4-yl)ethynyl]-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine

HRID 1253471ノート

反応式

HRID 1253471 の反応式
[C:1]([C:3]1[CH:4]=[N:5][N:6]2[CH:11]=[C:10]([C:12]3[CH:13]=[N:14][N:15]([CH3:17])[CH:16]=3)[CH:9]=[C:8]([O:18][CH3:19])[C:7]=12)#[CH:2].I[C:21]1[CH:22]=[N:23][N:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:25]=1[CH3:26].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>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.O1CCCC1>[CH3:19][O:18][C:8]1[C:7]2[N:6]([N:5]=[CH:4][C:3]=2[C:1]#[C:2][C:21]2[CH:22]=[N:23][N:24]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:25]=2[CH3:26])[CH:11]=[C:10]([C:12]2[CH:13]=[N:14][N:15]([CH3:17])[CH:16]=2)[CH:9]=1

参加物

6

反応物 3

HCID 2724141Tetrabutylammonium FluorideHCID 27764444-Iodo-5-methyl-1-phenyl-1H-pyrazoleHCID 584046903-ethynyl-4-methoxy-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine

生成物 1

HCID 584046694-methoxy-3-[(5-methyl-1-phenyl-1H-pyrazol-4-yl)ethynyl]-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine

試薬・触媒・溶媒 2

HCID 178418476HCID 178418476、化合物触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
80 °C

実験手順

3-ethynyl-4-methoxy-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine (30.0 mg, 0.119 mmol), 4-iodo-5-methyl-1-phenyl-1H-pyrazole (67.6 mg, 0.238 mmol), and bis(triphenylphosphine)palladium(II) chloride (8.4 mg, 0.012 mmol) were combined into one vial fitted with a Teflon septum. The vial was flushed with nitrogen and tetra-n-butylammonium fluoride (0.36 mL, 0.36 mmol, 1M in THF) and tetrahydrofuran (0.2 mL) were added. After sparging with nitrogen for 5 minutes, the reaction was heated to 80° C. for one hour. The reaction was cooled to ambient temperature, then diluted with ethyl acetate, and washed with saturated aqueous sodium bicarbonate. The organic layer was separated, and the aqueous layer was back extracted with ethyl acetate two times. The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was purified by preparative HPLC reverse phase (C-18), eluting with acetonitrile/water+0.05% TFA. The fractions containing product were combined and diluted in ethyl acetate, then washed with aqueous sodium bicarbonate and dried over sodium sulfate. The solution was filtered and concentrated under reduced pressure to give 4-methoxy-3-[(5-methyl-1-phenyl-1H-pyrazol-4-yl)ethynyl]-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine

後処理

  1. additionwere added
  2. customAfter sparging with nitrogen for 5 minutes
  3. temperatureThe reaction was cooled to ambient temperature
  4. additiondiluted with ethyl acetate
  5. washwashed with saturated aqueous sodium bicarbonate
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was back extracted with ethyl acetate two times
  8. dry with materialThe combined organic layers were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by preparative HPLC reverse phase (C-18)
  12. washeluting with acetonitrile/water+0.05% TFA
  13. additionThe fractions containing product
  14. additiondiluted in ethyl acetate
  15. washwashed with aqueous sodium bicarbonate
  16. dry with materialdried over sodium sulfate
  17. filtrationThe solution was filtered
  18. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-fe4a9229f23944668219cdc314df689e
出典データセット
uspto-grants-2013_06
特許番号
US08455477B2

反応ノート

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