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 1256845ノート

反応式

HRID 1256845 の反応式
[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

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
-20 °C

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-a976606dfdd04d45b354f1a9862182f3
出典データセット
uspto-grants-2013_06
特許番号
US08461169B2

反応ノート

読み込み中…