Dimethylformamide → 2-(6-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)-amide

HRID 246264

반응식

HRID 246264 반응식
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([Sn](CCCC)(CCCC)CCCC)=[N:7][NH:8]2)=[CH:4][CH:3]=1.[CH3:24][CH:25]([NH:33][C:34]([C:36]1[C:44]2[C:39](=[N:40][CH:41]=[C:42](Br)[N:43]=2)[N:38]([CH2:46][O:47][CH2:48][CH2:49][Si:50]([CH3:53])([CH3:52])[CH3:51])[CH:37]=1)=[O:35])[CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=1.CN(C=O)C>CCOCC.[Cu]I.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>[CH3:24][CH:25]([NH:33][C:34]([C:36]1[C:44]2[C:39](=[N:40][CH:41]=[C:42]([C:6]3[C:5]4[C:9](=[CH:10][C:2]([F:1])=[CH:3][CH:4]=4)[NH:8][N:7]=3)[N:43]=2)[N:38]([CH2:46][O:47][CH2:48][CH2:49][Si:50]([CH3:52])([CH3:51])[CH3:53])[CH:37]=1)=[O:35])[CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=1

참가 물질

7

반응물 3

HCID 6228DimethylformamideHCID 866779692-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)-amideHCID 1784482326-fluoro-3-(tributylstannyl)-1H-indazole

생성물 1

HCID 712857502-(6-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)-amide수율 61%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 3283Diethyl Ether용매

반응 조건

온도
90 °C

실험 절차

6-Fluoro-3-tributylstannyl-1H-indazole (0.20 g, 0.47 mmol), copper(I) iodide (12 mg, 0.06 mmol) and 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)-amide (200 mg, 0.41 mmol) were combined with DMF (6 mL) to give a yellow solution. The mixture was degassed with nitrogen for 10 min then tetrakis(triphenylphosphine)palladium (0) (23 mg, 0.02 mmol) was added. The reaction was stirred at 90° C. under nitrogen for 15 h. The reaction mixture was cooled, diluted with ether (60 mL) and washed with water and brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (0-3% methanol in dichloromethane with 0.5% ammonium hydroxide) to give 136 mg (61%) of 2-(6-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-methyl-2-pyridin-2-yl-ethyl)-amide as a foaming solid. MS: (M+H)+=546.

후처리

  1. customto give a yellow solution
  2. customThe mixture was degassed with nitrogen for 10 min
  3. temperatureThe reaction mixture was cooled
  4. washwashed with water and brine
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel chromatography (0-3% methanol in dichloromethane with 0.5% ammonium hydroxide)

출처 및 근거

ORD 기록
ord-c603173ada864d6d82a7bf8787b902a7
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

연결된 노트

불러오는 중…