3,4-dihydro-2H-pyran → methyl 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carboxylate

HRID 2367695ノート

反応式

HRID 2367695 の反応式
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[C:5]2[C:11]([O:13][CH3:14])=[O:12].C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1.[O:32]1[CH:37]=[CH:36][CH2:35][CH2:34][CH2:33]1>ClC(Cl)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:33]1[CH2:34][CH2:35][CH2:36][CH2:37][O:32]1)[N:6]=[C:5]2[C:11]([O:13][CH3:14])=[O:12]

参加物

5

反応物 3

HCID 80803,4-dihydro-2H-pyranHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 12689298Methyl 5-bromo-1H-indazole-3-carboxylate

生成物 1

HCID 69803802methyl 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carboxylate収率 82%

試薬・触媒・溶媒 1

HCID 63651,1-Dichloroethane溶媒

実験手順

A suspension of methyl 5-bromo-1H-indazole-3-carboxylate (CXVI) (1.35 g, 5.29 mmol), pyridinium p-toluenesulfonate (0.143 g, 0.56 mmol) and 3,4 dihydro-2H-pyran (1.02 mL, 11.90 mmol) in anhydrous dichloroethane (20 mL) was refluxed 5 h under argon. The suspension was turned into the clear solution. The solution was cooled and the excess solvent was evaporated under vacuum. The residue was dissolved in EtOAc and washed with dilute NaHCO3 solution (satd. NaHCO3 soln/H2O: 1:9). The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography (100% hexanes→5:95 EtOAc:hexanes) to get methyl 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carboxylate (CXVII) as a white solid (1.47 g, 4.34 mmol, 82% yield). 1H NMR (DMSO-d6) δ ppm 8.22 (d, J=1.4 Hz, 1H), 7.89 (d, J=7.2 Hz, 1H), 7.68 (dd, J=7.2, 1.6 Hz, 1H), 6.02 (dd, J=8.0, 2.4 Hz, 1H), 3.94 (s, 3H), 3.88 (m, 1H), 3.79 (m, 1H), 2.37-2.31 (m, 1H), 2.05-1.96 (m, 2H), 1.77-1.73 (m, 1H). 1.60-1.58 (m, 2H); ESIMS found for C14H15BrN2O3 m/z 340.0 (M+H).

後処理

  1. temperaturewas refluxed 5 h under argon
  2. temperatureThe solution was cooled
  3. customthe excess solvent was evaporated under vacuum
  4. dissolutionThe residue was dissolved in EtOAc
  5. washwashed with dilute NaHCO3 solution (
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography (100% hexanes→5:95 EtOAc:hexanes)

出典と根拠

ORDレコード
ord-a04b62ce8fda411ca55e3e4cd63f736d
出典データセット
uspto-grants-2014_04
特許番号
US08697887B2

反応ノート

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