Water → 2-(5-cyano-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

HRID 246294

反応式

HRID 246294 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].[CH3:26][N:27]1[C:35]2[C:30](=[CH:31][C:32]([C:36]#[N:37])=[CH:33][CH:34]=2)[C:29]([Sn](CCCC)(CCCC)CCCC)=[N:28]1.O.C(OCC)C>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:29]3[C:30]4[C:35](=[CH:34][CH:33]=[C:32]([C:36]#[N:37])[CH:31]=4)[N:27]([CH3:26])[N:28]=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

8

反応物 4

HCID 962WaterHCID 3283Diethyl EtherHCID 712799231-methyl-3-tributylstannanyl-1H-indazole-5-carbonitrileHCID 715756452-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

生成物 1

HCID 712803922-(5-cyano-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide収率 72%

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 50 ml round-bottomed flask, 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (300 mg, 0.70 mmol) and 1-methyl-3-tributylstannyl-1H-indazole-5-carbonitrile (crude from Step 3, 847 mg, 1.14 mmol) were dissolved in DMF (6.6 ml). The reaction mixture was evacuated and backfilled with argon then tetrakis(triphenylphosphine)palladium (0) (41 mg, 0.036 mmol) and copper (I) iodide (27 mg, 0.14 mmol) were added. The reaction mixture was stirred at 80° C. overnight then cooled to room temperature and water and diethyl ether were added. The resulting brown precipitate was collected via filtration washing with water and diethyl ether. The brown powder was absorbed on silica gel and chromatographed with MeOH/CH2Cl2/0.5% NH4OH (gradient: 0-2% MeOH) to afford 254 mg (72%) of 2-(5-cyano-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-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. temperaturethen cooled to room temperature
  3. filtrationThe resulting brown precipitate was collected via filtration
  4. washwashing with water and diethyl ether
  5. customThe brown powder was absorbed on silica gel
  6. customchromatographed with MeOH/CH2Cl2/0.5% NH4OH (gradient: 0-2% MeOH)

出典と根拠

ORDレコード
ord-df763a4f79244485ac543daaa8dccf14
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…