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Sodium hydride → 6-(1-methyl-1H-pyrazol-4-yl)-3-((S)-1-{2-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-2H-indazol-5-yl}-ethyl)imidazo[1,2-b]pyridazine

HRID 69276
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HRID 69276 반응식
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[CH:9][C:10]3[N:11]([C:13]([C@H:16]([C:18]4[CH:19]=[C:20]5[C:24](=[CH:25][CH:26]=4)[N:23]([CH2:27][CH2:28][O:29][CH:30]4[CH2:35][CH2:34][CH2:33][CH2:32][O:31]4)[N:22]=[CH:21]5)[CH3:17])=[CH:14][N:15]=3)[N:12]=2)[CH:4]=[N:3]1.[H-].[Na+].BrCCOC1CCCCO1>C1COCC1.C(Cl)Cl>[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[CH:9][C:10]3[N:11]([C:13]([C@H:16]([C:18]4[CH:19]=[CH:20][C:21]5[C:25](=[CH:24][N:23]([CH2:27][CH2:28][O:29][CH:30]6[CH2:35][CH2:34][CH2:33][CH2:32][O:31]6)[N:22]=5)[CH:26]=4)[CH3:17])=[CH:14][N:15]=3)[N:12]=2)[CH:4]=[N:3]1
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참가 물질

6

반응물 3

HCID 24758Sodium hydrideHCID 866212-(2-Bromoethoxy)tetrahydro-2H-pyranHCID 686322276-(1-Methyl-1H-pyrazol-4-yl)-3-((S)-1-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-indazol-5-yl}-ethyl)-imidazo[1,2-b]pyridazine

생성물 1

HCID 686342906-(1-methyl-1H-pyrazol-4-yl)-3-((S)-1-{2-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-2H-indazol-5-yl}-ethyl)imidazo[1,2-b]pyridazine

시약·촉매·용매 2

HCID 6344
Dichloromethane
용매
HCID 8028Tetrahydrofuran용매

실험 절차

6-(1-Methyl-1H-pyrazol-4-yl)-3-((S)-1-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-indazol-5-yl}-ethyl)-imidazo[1,2-b]pyridazine (Example 195, 34 mg, 0.1 mmol) was added to a suspension of NaH (55%, 4.8 mg 0.11 mmol) in dry THF (0.5 mL) at 0° C. The RM was allowed to stir at rt for 15 min and 2-(2-bromo-ethoxy)-tetrahydro-pyran (0.024 mL, 0.150 mmol) was added at 0° C. It was stirred additionally 7 h at rt, then overnight at 60° C., and finally 7 h at 120° C. in a pressure safe capped vial. After cooling at rt the RM was taken-up in DCM, washed with brine, the organic phase was dried over MgSO4 and concentrated under reduced pressure. The residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, EtOAc/MeOH=100:0->80:20) to afford 6-(1-methyl-1H-pyrazol-4-yl)-3-((S)-1-{2-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-2H-indazol-5-yl}-ethyl)imidazo[1,2-b]pyridazine and the title compound (tR 4.05 min (conditions 2), MH+=472.3).

후처리

  1. stirringIt was stirred additionally 7 h at rt
  2. customovernight at 60° C., and finally 7 h at 120° C. in a pressure safe capped vial
  3. temperatureAfter cooling at rt the RM
  4. washwashed with brine
  5. dry with materialthe organic phase was dried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, EtOAc/MeOH=100:0->80:20)

출처 및 근거

ORD 기록
ord-e9e4e70efad8413a81f98e5db3212071
출처 데이터셋
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08822468B2

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