Water → tert-butyl 3-(4-bromo-3-(5-fluoro-1-methylindolin-6-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl)azetidine-1-carboxylate

HRID 331015노트

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HRID 331015 반응식
[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]3[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13]3)[CH:9]=[C:10](I)[C:3]=12.Cl.[F:24][C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][C:33]=1B1OC(C)(C)C(C)(C)O1)[N:30]([CH3:43])[CH2:29][CH2:28]2.C(=O)([O-])[O-].[Na+].[Na+].O>COCCOC.CO.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]3[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13]3)[CH:9]=[C:10]([C:33]3[CH:32]=[C:31]4[C:27]([CH2:28][CH2:29][N:30]4[CH3:43])=[CH:26][C:25]=3[F:24])[C:3]=12

참가 물질

8

반응물 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 86720286tert-butyl 3-(4-bromo-3-iodo-1H-pyrrolo[2,3-b]pyridin-1-yl)azetidine-1-carboxylateHCID 1317319925-Fluoro-1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indoline, hydrochloride

생성물 1

HCID 71090156tert-butyl 3-(4-bromo-3-(5-fluoro-1-methylindolin-6-yl)-1H-pyrrolo[2,3-b]pyridin-1-yl)azetidine-1-carboxylate수율 67.8%

시약·촉매·용매 3

HCID 178418476HCID 178418476, 화합물촉매HCID 887Methanol용매HCID 80711,2-Dimethoxyethane용매

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온도
60 °C

실험 절차

To a mixture of tert-butyl 3-(4-bromo-3-iodo-1H-pyrrolo[2,3-b]pyridin-1-yl)azetidine-1-carboxylate (D31) (118 mg, 0.247 mmol), 5-fluoro-1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indoline, hydrochloride (85 mg, 0.271 mmol) in DME (2 mL) and MeOH (0.222 mL) was added bis(triphenylphosphine)palladium(II) chloride (17.32 mg, 0.025 mmol) and 2M sodium carbonate aq. solution (1.234 mL, 2.468 mmol). The mixture was stirred at 60° C. for 1 hour. The mixture was cooled to RT. Water (30 mL) was added and was extracted with ethyl acetate (3×50 mL). The combined organics were dried over magnesium sulfate, filtered and solvent removed in vacuo to give a residue which was purified on normal phase chromatography eluting with ethyl acetate in cyclohexane (0-50%) to give the title compound (84 mg). LCMS (A): m/z (M+H)+ 501/503, C24H26BrFN4O2 requires 500/502 (acidic).

후처리

  1. temperatureThe mixture was cooled to RT
  2. extractionwas extracted with ethyl acetate (3×50 mL)
  3. dry with materialThe combined organics were dried over magnesium sulfate
  4. filtrationfiltered
  5. customsolvent removed in vacuo
  6. customto give a residue which
  7. customwas purified on normal phase chromatography
  8. washeluting with ethyl acetate in cyclohexane (0-50%)

출처 및 근거

ORD 기록
ord-a727b0d05358407b8d83222977f9d595
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08877742B2

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