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

HRID 246389

반응식

HRID 246389 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.[CH3:21][O:22][C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][CH:31]=1)[N:28]([CH3:32])[N:27]=[C:26]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>[CH3:21][O:22][C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][CH:31]=1)[N:28]([CH3:32])[N:27]=[C:26]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 712803595-methoxy-1-methyl-3-(tributylstannyl)-1H-indazole

생성물 1

HCID 866779772-(5-methoxy-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde수율 82.2%

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

In a 25 mL round-bottomed flask, 2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (439 mg, 1.23 mmol) and 5-methoxy-1-methyl-3-(tributylstannyl)-1H-indazole (556 mg, 1.23 mmol) were dissolved in DMF (3.00 mL) under argon, tetrakis(triphenylphosphine)palladium (0) (71.2 mg, 61.6 μmol) and CuI (46.9 mg, 246 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-methoxy-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (443 mg, 1.01 mmol, 82.2%) as a yellow solid. MS (M+H)+=438 (>90% purity); 1H NMR (CDCl3) δ: 10.50 (s, 1H), 9.34 (s, 1H), 8.37 (d, J=2.3 Hz, 1H), 8.30 (s, 1H), 7.39 (d, J=9.1 Hz, 1H), 7.19 (dd, J=9.1, 2.3 Hz, 1H), 5.80 (s, 2H), 4.21 (s, 3H), 4.07 (s, 3H), 3.59-3.73 (m, 2H), 0.91-1.06 (m, 2H), 0.00 (s, 8H).

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-450f3bafc3174d3f939be9ef6da1698d
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

연결된 노트

불러오는 중…