Sodium Bicarbonate → 2-Methyl-5-oxo-4-{3-[6-(propan-2-yloxy)pyridin-3-yl}-1H-indazol-5-yl]-1,4,5,7-tetrahydrofuro-[3,4-b]pyridine-3-carbonitrile

HRID 408558노트

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HRID 408558 반응식
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH:11]3[C:16]([C:17]#[N:18])=[C:15]([CH3:19])[NH:14][C:13]4[CH2:20][O:21][C:22](=[O:23])[C:12]3=4)[CH:9]=2)[NH:4][N:3]=1.[CH3:24][CH:25]([O:27][C:28]1[N:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1)[CH3:26].C(=O)(O)[O-].[Na+]>O1CCOCC1.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>[CH3:19][C:15]1[NH:14][C:13]2[CH2:20][O:21][C:22](=[O:23])[C:12]=2[CH:11]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[NH:4][N:3]=[C:2]3[C:31]2[CH:32]=[N:33][C:28]([O:27][CH:25]([CH3:26])[CH3:24])=[CH:29][CH:30]=2)[C:16]=1[C:17]#[N:18]

참가 물질

6

반응물 3

HCID 516892Sodium BicarbonateHCID 44754864[6-(Propan-2-yloxy)pyridin-3-yl]boronic acidHCID 178428406HCID 178428406, 화합물

생성물 1

HCID 469112702-Methyl-5-oxo-4-{3-[6-(propan-2-yloxy)pyridin-3-yl}-1H-indazol-5-yl]-1,4,5,7-tetrahydrofuro-[3,4-b]pyridine-3-carbonitrile수율 19.6%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

To a degassed solution of 120 mg (0.323 mmol) 4-(3-bromo-1H-indazol-5-yl)-2-methyl-5-oxo-1,4,5,7-tetrahydrofuro[3,4-b]pyridine-3-carbonitrile (Example 24) and 70.2 mg (0.388 mmol) [6-(propan-2-yloxy)pyridin-3-yl]boronic acid in anhydrous 1,4-dioxane (3.5 ml) were added under inert gas atmosphere 37.4 mg (0.032 mmol) tetrakis(triphenylphosphine)palladium(0) and aqueous sodium bicarbonate solution (2 M, 0.77 ml). The resulting mixture was stirred at 100° C. for 12 h. After cooling to room temperature and concentration under reduced pressure, the remaining solid was dissolved in ethyl acetate (20 ml). The solution was subsequently washed with water and brine, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by preparative RP-HPLC (acetonitrile/water gradient, final mixture 95:5 v/v) to yield the title compound as a white solid (27 mg, 19% of th.).

후처리

  1. temperatureAfter cooling to room temperature
  2. concentrationconcentration under reduced pressure
  3. dissolutionthe remaining solid was dissolved in ethyl acetate (20 ml)
  4. washThe solution was subsequently washed with water and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by preparative RP-HPLC (acetonitrile/water gradient, final mixture 95:5 v/v)

출처 및 근거

ORD 기록
ord-b9d2cb5b011247199a4fa4f996baa603
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759341B2

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