2-ethyl-5-(4-fluoro-benzylamino)-2H-pyrazole-3-carbaldehyde → (5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-[2-ethyl-5-(4-fluoro-benzylamino)-2H-pyrazol-3-yl]-methanol

HRID 1754792笔记

反应方程式

HRID 1754792 反应方程式
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10](I)=[CH:9][N:8]([Si](C(C)C)(C(C)C)C(C)C)[C:5]2=[N:6][CH:7]=1.C([Mg]Cl)(C)C.[CH2:27]([N:29]1[C:33]([CH:34]=[O:35])=[CH:32][C:31]([NH:36][CH2:37][C:38]2[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=2)=[N:30]1)[CH3:28]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([CH:34]([C:33]3[N:29]([CH2:27][CH3:28])[N:30]=[C:31]([NH:36][CH2:37][C:38]4[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=4)[CH:32]=3)[OH:35])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

参与物

5

反应物 3

HCID 576192072-ethyl-5-(4-fluoro-benzylamino)-2H-pyrazole-3-carbaldehydeHCID 580879285-chloro-3-iodo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridineHCID 178418918HCID 178418918，化合物

产物 1

HCID 57619398(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-[2-ethyl-5-(4-fluoro-benzylamino)-2H-pyrazol-3-yl]-methanol收率 55.9%

试剂、催化剂与溶剂 1

HCID 8028四氢呋喃溶剂3 次

反应条件

温度
-20 °C

实验过程

5-Chloro-3-iodo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (629, 0.15 g, 0.34 mmol) was dissolved in tetrahydrofuran (3 mL, 40 mmol) and the solution was cooled to −20° C. 2 M isopropylmagnesium chloride in tetrahydrofuran (200 μL) was added dropwise and the reaction was stirred and allowed to warm to −5° C. After the reaction was cooled to −20° C., 2-ethyl-5-(4-fluoro-benzylamino)-2H-pyrazole-3-carbaldehyde (530, 0.043 g, 0.17 mmol, prepared as described in Example 47, Scheme 162, Step 5) in tetrahydrofuran (4 mL) was added to the mixture. The reaction was stirred to −5° C., then concentrated, ethyl acetate was added and the mixture was washed with sodium bicarbonate saturated solution and brine. After drying over anhydrous sodium sulfate, the solvent was removed under reduced pressure. Purification with silica gel column chromatography eluting with a gradient of ethyl acetate (5-80%) in hexanes gave the desired compound (630, 0.038 g, 40%).

后处理

  1. temperatureto warm to −5° C
  2. temperatureAfter the reaction was cooled to −20° C.
  3. stirringThe reaction was stirred to −5° C.
  4. concentrationconcentrated
  5. additionethyl acetate was added
  6. washthe mixture was washed with sodium bicarbonate saturated solution and brine
  7. dry with materialAfter drying over anhydrous sodium sulfate
  8. customthe solvent was removed under reduced pressure
  9. customPurification with silica gel column chromatography
  10. washeluting with a gradient of ethyl acetate (5-80%) in hexanes

来源与证据

ORD记录
ord-7c8efe1e47e442e0a0b8feeda7b7d388
来源数据集
uspto-grants-2015_10
专利号
US09169250B2

反应笔记

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