2-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide → HCID 178449394、化合物

HRID 246313

反応式

HRID 246313 の反応式
[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14](Br)[N:15]=2)[N:10]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:26]([SiH2:30][O:31][C:32]([CH3:56])([CH3:55])[C:33]1[CH:34]=[CH:35][CH:36]=[C:37]2[C:41]=1[NH:40][N:39]=[C:38]2[Sn](CCCC)(CCCC)CCCC)([CH3:29])([CH3:28])[CH3:27]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:38]3[C:37]4[C:41](=[C:33]([C:32]([CH3:56])([CH3:55])[O:31][SiH2:30][C:26]([CH3:29])([CH3:28])[CH3:27])[CH:34]=[CH:35][CH:36]=4)[NH:40][N:39]=3)[N:15]=2)[N:10]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

6

反応物 2

HCID 715756452-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideHCID 178448228HCID 178448228、化合物

生成物 1

HCID 178449394HCID 178449394、化合物収率 34%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418397HCID 178418397、化合物触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

実験手順

In a 25 ml round-bottomed flask, 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (180 mg, 0.42 mmol) and 7-(tert-butyldimethyl-silanyloxymethyl)-3-tributylstannanyl-1H-indazole (crude from Step 4, 462 mg, 0.50 mmol) were dissolved in DMF (2.8 ml). The reaction mixture was evacuated and backfilled with argon and tetrakis(triphenylphosphine)palladium (0) (25 mg, 0.022 mmol) and copper (I) iodide (16 mg, 0.084 mmol) were added. The reaction mixture was stirred at 80° C. overnight then cooled to room temperature, quenched with water and extracted with diethyl ether (2×). The combined organic layers were washed twice with water and once with brine then concentrated. The residue was chromatographed over 25 g silica gel with EtOAc/hexanes (gradient: 0-30% EtOAc) to afford 86 mg (34%) of 2-[7-(tert-butyl-dimethyl-silanyloxymethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as a light yellow solid.

後処理

  1. customThe reaction mixture was evacuated
  2. additionwere added
  3. temperaturethen cooled to room temperature
  4. customquenched with water
  5. extractionextracted with diethyl ether (2×)
  6. washThe combined organic layers were washed twice with water and once with brine
  7. concentrationthen concentrated
  8. customThe residue was chromatographed over 25 g silica gel with EtOAc/hexanes (gradient: 0-30% EtOAc)

出典と根拠

ORDレコード
ord-4fa93ed065c14364b79fe924fae5db38
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

関連ノート

読み込み中…