1,2-Dimethoxyethane → tert-butyl (3S)-3-[6-(5-methyl-1H-pyrazol-4-yl)-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl]-2-azabicyclo[2.2.2]octane-2-carboxylate

HRID 1052191ノート

反応式

HRID 1052191 の反応式
Br[C:2]1[S:10][C:9]2[C:8](=[O:11])[NH:7][C:6]([C@@H:12]3[CH:17]4[CH2:18][CH2:19][CH:14]([CH2:15][CH2:16]4)[N:13]3[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[N:5][C:4]=2[CH:3]=1.[CH3:27][C:28]1[C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][N:30](C(OC(C)(C)C)=O)[N:29]=1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>O>[CH3:27][C:28]1[NH:29][N:30]=[CH:31][C:32]=1[C:2]1[S:10][C:9]2[C:8](=[O:11])[NH:7][C:6]([C@@H:12]3[CH:17]4[CH2:18][CH2:19][CH:14]([CH2:15][CH2:16]4)[N:13]3[C:20]([O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21])=[N:5][C:4]=2[CH:3]=1

参加物

6

反応物 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 53216815Tert-butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-pyrazole-1-carboxylateHCID 136333933tert-butyl (3S)-3-(6-bromo-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)-2-azabicyclo[2.2.2]octane-2-carboxylate

生成物 1

HCID 136333934tert-butyl (3S)-3-[6-(5-methyl-1H-pyrazol-4-yl)-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl]-2-azabicyclo[2.2.2]octane-2-carboxylate収率 76.6%

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
100 °C

実験手順

tert-Butyl(3S)-3-(6-Bromo-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)-2-azabicyclo[2.2.2]octane-2-carboxylate (190 mg), tert-butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (266 mg), sodium carbonate (78 mg), 1,2-dimethoxyethane (3.0 mL) and water (1.5 mL) were placed in a flask, and the atmosphere in the flask was purged with argon. [1,1′-Bis(diphenylphosphino)ferrocene]palladium(II) dichloride-dichloromethane complex (1:1) (35 mg) was added, and the atmosphere in the flask was purged again with argon. The reaction system was stirred at 100° C. for 3 hr, and the mixture was extracted with ethyl acetate and dried over anhydrous sodium sulfate. Insoluble material was removed by filtration, and the extract was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane), and the obtained pale-yellow solid was crystallized from methanol/ethyl acetate to give the title compound (146 mg) as a pale-yellow solid.

後処理

  1. customthe atmosphere in the flask was purged with argon
  2. addition[1,1′-Bis(diphenylphosphino)ferrocene]palladium(II) dichloride-dichloromethane complex (1:1) (35 mg) was added
  3. customthe atmosphere in the flask was purged again with argon
  4. extractionthe mixture was extracted with ethyl acetate
  5. dry with materialdried over anhydrous sodium sulfate
  6. customInsoluble material was removed by filtration
  7. concentrationthe extract was concentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)
  9. customthe obtained pale-yellow solid was crystallized from methanol/ethyl acetate

出典と根拠

ORDレコード
ord-355acf34fbc24a6683e1748e2877be2c
出典データセット
uspto-grants-2016_07
特許番号
US09388195B2

反応ノート

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