2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde → 2-(4,6-difluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

HRID 246067

반응식

HRID 246067 반응식
Br[C:2]1[N:3]=[C:4]2[C:10]([CH:11]=[O:12])=[CH:9][N:8]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:5]2=[N:6][CH:7]=1.[F:21][C:22]1[CH:30]=[C:29]([F:31])[CH:28]=[C:27]2[C:23]=1[C:24]([Sn](CCCC)(CCCC)CCCC)=[N:25][NH:26]2>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>[F:21][C:22]1[CH:30]=[C:29]([F:31])[CH:28]=[C:27]2[C:23]=1[C:24]([C:2]1[N:3]=[C:4]3[C:10]([CH:11]=[O:12])=[CH:9][N:8]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:5]3=[N:6][CH:7]=1)=[N:25][NH:26]2

참가 물질

6

반응물 2

HCID 578296122-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehydeHCID 178448233HCID 178448233, 화합물

생성물 1

HCID 866779412-(4,6-difluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde수율 100.5%

시약·촉매·용매 3

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

실험 절차

In a round-bottomed flask, 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (1.56 g, 4.38 mmol) and 4,6-difluoro-3-tributylstannanyl-1H-indazole (1.94 g, 4.38 mmol) were dissolved in DMF (40 mL) and tetrakis(triphenylphosphine)palladium(0) (253 mg, 0.22 mmol) and copper(I) iodide (167 mg, 0.88 mmol) were added. The reaction mixture was purged with argon, stirred at room temperature for 4 h, then heated at 80° C. for 1 h. The reaction was cooled to room temperature, quenched with sat NH4Cl and extracted with EtOAc (2×). The combined organics were washed with sat LiCl and brine then dried over MgSO4 and concentrated. The crude residue was purified by silica gel chromatography with 50% to 100% EtOAc/heptane to provide 1.89 g of 2-(4,6-difluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde as a brown solid.

후처리

  1. customThe reaction mixture was purged with argon
  2. temperatureheated at 80° C. for 1 h
  3. temperatureThe reaction was cooled to room temperature
  4. customquenched with sat NH4Cl
  5. extractionextracted with EtOAc (2×)
  6. washThe combined organics were washed with sat LiCl and brine
  7. dry with materialthen dried over MgSO4
  8. concentrationconcentrated
  9. customThe crude residue was purified by silica gel chromatography with 50% to 100% EtOAc/heptane

출처 및 근거

ORD 기록
ord-5f7c9fb6425140b49d462ba7f9263305
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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