Water → tert-butyl N-[7-(2,4-dimethoxy-6-methylphenyl)-2-methoxypyrazolo[1,5-a]pyridin-3-yl)-N-tetrahydro-2-furanylmethylcarbamate

HRID 1865030ノート

反応式

HRID 1865030 の反応式
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[C:5]([CH3:11])[C:4]=1[C:12]1[N:17]2[N:18]=[C:19]([O:29][CH3:30])[C:20]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[C:16]2[CH:15]=[CH:14][CH:13]=1.[H-].[Na+].[O:33]1[CH2:37][CH2:36][CH2:35][CH:34]1[CH2:38]Cl.O>CN(C)C=O.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[C:5]([CH3:11])[C:4]=1[C:12]1[N:17]2[N:18]=[C:19]([O:29][CH3:30])[C:20]([N:21]([CH2:38][CH:34]3[CH2:35][CH2:36][CH2:37][O:33]3)[C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:25])[CH3:26])=[C:16]2[CH:15]=[CH:14][CH:13]=1

参加物

7

反応物 4

HCID 962WaterHCID 181502-Chloromethyl tetrahydrofuranHCID 24758Sodium hydrideHCID 21984512tert-butyl N-[7-(2,4-dimethoxy-6-methylphenyl)-2-methoxypyrazolo[1,5-a]pyridin-3-yl]carbamate

生成物 1

HCID 21984687tert-butyl N-[7-(2,4-dimethoxy-6-methylphenyl)-2-methoxypyrazolo[1,5-a]pyridin-3-yl)-N-tetrahydro-2-furanylmethylcarbamate

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
60 °C

実験手順

After dissolving tert-butyl N-[7-(2,4-dimethoxy-6-methylphenyl)-2-methoxypyrazolo[1,5-a]pyridin-3-yl]carbamate (50 mg) in N,N-dimethylformamide (2 mL), sodium hydride (60%, 15 mg) was added while cooling on ice, and then 2-tetrahydrofuranylmethyl chloride (16 μL) was added and the mixture was stirred for 3 hours at 60° C. under a nitrogen stream. Water was added to the reaction mixture, extraction was performed with ethyl acetate and the extract washed with brine. After drying over anhydrous magnesium sulfate and filtration, the solvent was concentrated under reduced pressure to obtain tert-butyl N-[7-(2,4-dimethoxy-6-methylphenyl)-2-methoxypyrazolo[1,5-a]pyridin-3-yl]-N-tetrahydro-2-furanylmethylcarbamate. The crude product was dissolved in ethyl acetate (2 mL) without purification, a 4 N hydrochloric acid/ethyl acetate solution (4 mL) was added, and the mixture was stirred at 40° C. for 1 hour. The reaction mixture was neutralized with 5 N aqueous sodium hydroxide while cooling on ice, and then extraction was performed with ethyl acetate and the organic layer washed with water and brine. The obtained organic layer was dried over anhydrous magnesium sulfate and filtered, and the solvent was concentrated under reduced pressure to obtain N-[7-(2,4-dimethoxy-6-methylphenyl)-2-methoxypyrazolo[1,5-a]pyridin-3-yl]-N-tetrahydro-2-furanylmethylamine as a crude product. This was dissolved in tetrahydrofuran (2 mL) without purification, and after adding cyclopropanecarboxyaldehyde (27 μL) and 3 M aqueous sulfuric acid (0.121 mL), sodium borohydride (9 mg) was added in five portions while vigorously stirring on ice, and stirring was continued for 30 minutes. Saturated aqueous sodium hydrogencarbonate was added to the reaction mixture, extraction was performed with ethyl acetate, the solvent was concentrated, the residue was purified by silica gel column chromatography, and the title compound (31 mg) was obtained from the n-hexane:ethyl acetate (5:1) fraction as a yellow oil.

後処理

  1. additionwas added
  2. temperaturewhile cooling on ice
  3. washthe extract washed with brine
  4. dry with materialAfter drying over anhydrous magnesium sulfate and filtration
  5. concentrationthe solvent was concentrated under reduced pressure

出典と根拠

ORDレコード
ord-f9131f8499fe478f9ed996a4e544e9af
出典データセット
uspto-grants-2009_12
特許番号
US07625925B2

反応ノート

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