2-(1-Methyl-1H-pyrazolo[4,3-b]pyridin-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide → 2-(1-methyl-1H-pyrazolo[4,3-b]pyridin-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

HRID 246290

反応式

HRID 246290 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(C1CN(C(=O)[C@H](NC(C2C3C(=NC=C([C:47]4[C:51]5=[N:52][CH:53]=[CH:54][CH:55]=[C:50]5[N:49]([CH3:56])[N:48]=4)N=3)NC=2)=O)C)C1)#N>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:47]3[C:51]4=[N:52][CH:53]=[CH:54][CH:55]=[C:50]4[N:49]([CH3:56])[N:48]=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 712886732-(1-Methyl-1H-pyrazolo[4,3-b]pyridin-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amideHCID 715756452-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

生成物 1

HCID 712796112-(1-methyl-1H-pyrazolo[4,3-b]pyridin-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide収率 41%

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 round-bottomed flask, 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (110 mg, 0.26 mmol) and 1-methyl-3-tributylstannyl-1H-pyrazolo[4,3-b]pyridine (see Example 98, 340 mg, 0.40 mmol) were dissolved in DMF (2.4 ml). The reaction mixture was evacuated and backfilled with argon then tetrakis(triphenylphosphine)palladium (0) (15 mg, 0.013 mmol) and copper (I) iodide (10 mg, 0.053 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 dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over 12 g silica gel with EtOAc/hexanes (gradient: 0-70% EtOAc) to afford 51 mg (41%) of 2-(1-methyl-1H-pyrazolo[4,3-b]pyridin-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. temperaturethen cooled to room temperature
  3. customquenched with water
  4. extractionextracted with diethyl ether (2×)
  5. washThe combined organic layers were washed twice with water and once with brine
  6. dry with materialthen dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was chromatographed over 12 g silica gel with EtOAc/hexanes (gradient: 0-70% EtOAc)

出典と根拠

ORDレコード
ord-b006fe7ef8c14181927952241a09c3e5
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

関連ノート

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