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Diisopropylamine → 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 1253472
ノート
印刷プレビュー

反応式

HRID 1253472 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].O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.C(NC(C)C)(C)C>[CH2-]C=C.[CH2-]C=C.Cl[Pd+].Cl[Pd+].[Cu]I.C(#N)C>[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
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 7912DiisopropylamineHCID 521585Tris(furan-2-yl)phosphaneHCID 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 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒
HCID 61538Palladium, di-mu-chlorobis(eta3-2-propenyl)di-触媒
HCID 6342Acetonitrile溶媒

反応条件

温度
45 °C

実験手順

3-ethynyl-4-methoxy-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine (20.0 mg, 0.079 mmol), 4-iodo-5-methyl-1-phenyl-1H-pyrazole (33.8 mg, 0.119 mmol), allylpalladium chloride dimer (2.9 mg, 7.93 mmol), tri(2-furyl)phosphine (3.7 mg, 0.016 mmol) and copper (I) iodide (0.8 mg, 4 mmol) were combined into one vial fitted with a Teflon septum. The vial was and flushed with nitrogen and acetonitrile (0.8 mL) and diisopropylamine (0.034 mL, 0.238 mmol) were added. After sparging with nitrogen for 5 minutes, the reaction was heated to 45° C. for one hour. The mixture was cooled to ambient temperature, 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 mixture 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-bcf2437118da41978fa4563930d23693
出典データセット
uspto-grants-2013_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08455477B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート