2-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide → 2-(5-difluoromethoxy-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

HRID 246396

반응식

HRID 246396 반응식
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11]([NH:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:9][N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:5]2=[N:6][CH:7]=1.[F:26][CH:27]([F:51])[O:28][C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][CH:37]=1)[NH:34][N:33]=[C:32]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>[C:14]([NH:13][C:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([C:32]3[C:31]4[C:35](=[CH:36][CH:37]=[C:29]([O:28][CH:27]([F:26])[F:51])[CH:30]=4)[NH:34][N:33]=3)[N:3]=2)[N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[CH:9]=1)=[O:12])([CH3:17])([CH3:16])[CH3:15]

참가 물질

6

반응물 2

HCID 715756452-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideHCID 1784482315-(difluoromethoxy)-3-(tributylstannyl)-1H-indazole

생성물 1

HCID 712795662-(5-difluoromethoxy-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide수율 58.3%

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-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (220 mg, 515 μmol) and 5-(difluoromethoxy)-3-(tributylstannyl)-1H-indazole (268 mg, 566 μmol.10) were dissolved in DMF (1.06 mL) under argon, tetrakis(triphenylphosphine)palladium (0) (29.7 mg, 25.7 μmol) and CuI (19.6 mg, 103 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 N-tert-butyl-2-(5-(difluoromethoxy)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (159 mg, 300 μmol, 58.2%) as an off-white solid. MS (M+Na)+=553 (>90% purity); 1H NMR (CDCl3) δ: 10.74 (br. s., 1H), 9.29 (s, 1H), 8.42 (s, 1H), 8.36 (d, J=2.3 Hz, 1H), 8.09 (s, 1H), 7.64 (d, J=9.1 Hz, 1H), 7.40 (dd, J=8.9, 2.1 Hz, 1H), 6.57 (t, J=74.0 Hz, 1H), 5.76 (s, 2H), 3.56-3.70 (m, 2H), 1.67 (s, 9H), 0.92-1.04 (m, 2H), 0.00 (s, 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-3880a073d6c24077b43f06172aa77a45
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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