2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde → 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

HRID 246377

반응식

HRID 246377 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][CH:22]([F:47])[O:23][C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[N:29]([CH3:33])[N:28]=[C:27]2[Sn](CCCC)(CCCC)CCCC>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:47][CH:22]([F:21])[O:23][C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[N:29]([CH3:33])[N:28]=[C:27]2[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

참가 물질

6

반응물 2

HCID 578296122-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehydeHCID 712796275-(Difluoromethoxy)-1-methyl-3-(tributylstannyl)-1H-indazole

생성물 1

HCID 866779762-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde수율 72.9%

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

2-Bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (224 mg, 629 μmol) and 5-(difluoromethoxy)-1-methyl-3-(tributylstannyl)-1H-indazole (398 mg, 818 μmol.30) were dissolved in DMF (3 mL) under argon, tetrakis(triphenylphosphine)palladium (0) (36.3 mg, 31.4 μmol) and CuI (24.0 mg, 126 μmol, Eq: 0.20) were added and the mixture sonicated for 5 min with bubbling argon. The reaction mixture was stirred at 90° C. (oil bath temperature) for 2.5 h. The reaction mixture was concentrated under high vacuum and the residue was purified by chromatography (80 g column, 50 μm from Analogix, 0-50% EtOAc in hexanes over 30 min) to give 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (217 mg, 458 μmol, 72.9%) as a light brown solid. MS (M+H)+=474; 1H NMR (CDCl3) δ: 10.51 (br. s., 1H), 9.29 (s, 1H), 8.61 (s, 1H), 8.30 (s, 1H), 7.38-7.52 (m, 1H), 7.27-7.36 (m, 1H), 6.69 (t, J=74.8 Hz, 1H), 5.76 (s, 2H), 4.20 (s, 3H), 3.56-3.70 (m, 2H), 0.91-1.02 (m, 2H), −0.08-0.06 (m, 9H).

후처리

  1. customthe mixture sonicated for 5 min with bubbling argon
  2. concentrationThe reaction mixture was concentrated under high vacuum
  3. customthe residue was purified by chromatography (80 g column, 50 μm from Analogix, 0-50% EtOAc in hexanes over 30 min)

출처 및 근거

ORD 기록
ord-cfb4e816e8c74c779b4b8ebdbfdd2b88
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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