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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
ノート
印刷プレビュー

反応式

HRID 69276 の反応式
[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
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 6344
Dichloromethane
溶媒
HCID 8028Tetrahydrofuran溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-e9e4e70efad8413a81f98e5db3212071
出典データセット
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08822468B2

反応ノート

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