3,4-dihydro-2H-pyran → 5-Bromo-4-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 1057113ノート

反応式

HRID 1057113 の反応式
[Br:1][C:2]1[C:3]([F:11])=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2.[O:12]1[CH:17]=[CH:16][CH2:15][CH2:14][CH2:13]1.C([O-])(O)=O.[Na+]>ClCCl.CC1C=CC(S(O)(=O)=O)=CC=1>[Br:1][C:2]1[C:3]([F:11])=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:13]1[CH2:14][CH2:15][CH2:16][CH2:17][O:12]1)[N:6]=[CH:5]2

参加物

6

反応物 3

HCID 80803,4-dihydro-2H-pyranHCID 516892Sodium BicarbonateHCID 454803935-Bromo-4-fluoro-1H-indazole

生成物 1

HCID 667933085-Bromo-4-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole収率 79.9%

試薬・触媒・溶媒 2

HCID 6101p-Toluenesulfonic acid触媒HCID 6344Dichloromethane溶媒

実験手順

To a mixture of 5-bromo-4-fluoro-1H-indazole (50 g, 0.23 mol) and 3,4-dihydro-2H-pyran (23 g, 0.28 mol) in dry dichloromethane (1000 mL) was added p-TsOH (2.2 g, 11.5 mmol) at room temperature. The resulting mixture was stirred overnight at that temperature. Upon completion, saturated aqueous NaHCO3 (100 mL) was added slowly into the reaction mixture. The organic layer was separated, dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (0˜2% EtOAc in petroleum ether) and then re-crystallized from petroleum ether to afford the title compound (55 g). 1H NMR (300 MHz, DMSO-d6): δ 8.28 (s, 1H), 7.58-7.66 (m, 2H), 5.89 (dd, 1H), 3.90-3.85 (m, 1H), 3.79-3.70 (m, 1H), 2.42-2.29 (m, 1H), 2.06-1.94 (m, 2H), 1.77-1.68 (m, 1H), 1.60-1.53 (m, 2H); LCMS: 299 (M+H)+.

後処理

  1. customThe organic layer was separated
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by column chromatography on silica gel (0˜2% EtOAc in petroleum ether)
  5. customre-crystallized from petroleum ether

出典と根拠

ORDレコード
ord-e197047612804b2da4313799b18ab378
出典データセット
uspto-grants-2016_07
特許番号
US09399646B2

反応ノート

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