2-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide → N-tert-butyl-2-[5-(2-tert-butylsilyloxypropan-2-yl)-1-methylindazol-3-yl]-5-(2-trimethylsilylethoxymethyl)pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246340

반응식

HRID 246340 반응식
[C:1]([SiH2:5][O:6][C:7]([CH3:32])([CH3:31])[C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[N:13]([CH3:17])[N:12]=[C:11]2[Sn](CCCC)(CCCC)CCCC)([CH3:4])([CH3:3])[CH3:2].[C:33]([NH:37][C:38]([C:40]1[C:48]2[C:43](=[N:44][CH:45]=[C:46](Br)[N:47]=2)[N:42]([CH2:50][O:51][CH2:52][CH2:53][Si:54]([CH3:57])([CH3:56])[CH3:55])[CH:41]=1)=[O:39])([CH3:36])([CH3:35])[CH3:34]>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:33]([NH:37][C:38]([C:40]1[C:48]2[C:43](=[N:44][CH:45]=[C:46]([C:11]3[C:10]4[C:14](=[CH:15][CH:16]=[C:8]([C:7]([CH3:32])([CH3:31])[O:6][SiH2:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH:9]=4)[N:13]([CH3:17])[N:12]=3)[N:47]=2)[N:42]([CH2:50][O:51][CH2:52][CH2:53][Si:54]([CH3:57])([CH3:56])[CH3:55])[CH:41]=1)=[O:39])([CH3:36])([CH3:35])[CH3:34]

참가 물질

6

반응물 2

HCID 715756452-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideHCID 173502725Tert-butyl-[2-(1-methyl-3-tributylstannylindazol-5-yl)propan-2-yloxy]silane

생성물 1

HCID 131731223N-tert-butyl-2-[5-(2-tert-butylsilyloxypropan-2-yl)-1-methylindazol-3-yl]-5-(2-trimethylsilylethoxymethyl)pyrrolo[2,3-b]pyrazine-7-carboxamide수율 74%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 6228Dimethylformamide용매

반응 조건

온도
90 °C

실험 절차

To a solution of 5-(tert-butyl-dimethyl-silanyloxymethyl)-1-methyl-3-tributylstannanyl-1H-indazole (265 mg, 0.47 mmol) and 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (100 mg, 0.23 mmol) in DMF (2 mL) were added Pd(PPh3)4 (14 mg, 0.012 mmol) and copper(I) iodide (9 mg, 0.047 mmol). The reaction mixture was heated at 90° C. for 1 h then cooled to room temperature, quenched with water and extracted with EtOAc (2×). The combined organics were washed with water (3×) and brine then dried over MgSO4 and concentrated. The residue was absorbed on silica gel and chromatographed with 20% to 50% EtOAc/hexanes to isolate 106 mg (73%) of 2-[5-(tert-butyldimethyl-silanyloxymethyl)-1-methyl-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as a beige solid.

후처리

  1. temperaturethen cooled to room temperature
  2. customquenched with water
  3. extractionextracted with EtOAc (2×)
  4. washThe combined organics were washed with water (3×) and brine
  5. dry with materialthen dried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was absorbed on silica gel
  8. customchromatographed with 20% to 50% EtOAc/hexanes

출처 및 근거

ORD 기록
ord-f094d95fad3c4c988ed85bbbd177127b
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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