Hydrochloric Acid → 1-Cylobutyl-N-{cis-6-[(4-hydroxytetrahydro-2H-pyran-4-yl)methyl]piperidin-3-yl}1H-indazole-3-carboxamide

HRID 602461ノート

反応式

HRID 602461 の反応式
[CH:1]1([N:5]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7]([C:14]([NH:16][C@H:17]3[CH2:22][N:21](C(OC(C)(C)C)=O)[C@@H:20]([CH2:30][C:31]4([OH:37])[CH2:36][CH2:35][O:34][CH2:33][CH2:32]4)[CH2:19][CH2:18]3)=[O:15])=[N:6]2)[CH2:4][CH2:3][CH2:2]1.Cl>CO>[CH:1]1([N:5]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7]([C:14]([NH:16][C@H:17]3[CH2:18][CH2:19][C@@H:20]([CH2:30][C:31]4([OH:37])[CH2:36][CH2:35][O:34][CH2:33][CH2:32]4)[NH:21][CH2:22]3)=[O:15])=[N:6]2)[CH2:2][CH2:3][CH2:4]1

参加物

4

反応物 2

HCID 313Hydrochloric AcidHCID 67270199tert-Butyl cis-5-{[(1-cyclobutyl-1H-indazol-3-yl)carbonyl]amino}-2-[(4-hydroxytetrahydro-2H-pyran-4-yl)methyl]piperidine-1-carboxylate

生成物 1

HCID 672701181-Cylobutyl-N-{cis-6-[(4-hydroxytetrahydro-2H-pyran-4-yl)methyl]piperidin-3-yl}1H-indazole-3-carboxamide収率 81%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

The mixture of tert-butyl cis-5-{[(1-cyclobutyl-1H-indazol-3-yl)carbonyl]amino}-2-[(4-hydroxytetrahydro-2H-pyran-4-yl)methyl]piperidine-1-carboxylate (112 mg, 0.22 mmol, step 3 of Example 4) and 10% hydrochloric acid in methanol (15 mL) was stirred at room temperature. After stirring for 1 h, the solvent was removed under reduced pressure. The residue was dissolved in methanol (2 mL), and this was poured onto saturated aqueous sodium hydrogencarbonate solution (50 mL). The aqueous layer was extracted with dichloromethane (50 mL×3). The combined organic layer was dried over magnesium sulfate, and concentrated under reduced pressure. The residue was chromatographed on a column of NH-silica gel eluting with ethyl acetate/n-hexane (5:1) to give 73 mg (81%) of the title compound as a colorless oil. This was treated with oxalic acid monohydrate (22 mg) in methanol (5 mL). The solvent was removed under reduced pressure to give 42 mg of the title compound as an ethanedioate salt as a white solid.

後処理

  1. stirringAfter stirring for 1 h
  2. customthe solvent was removed under reduced pressure
  3. dissolutionThe residue was dissolved in methanol (2 mL)
  4. additionthis was poured onto saturated aqueous sodium hydrogencarbonate solution (50 mL)
  5. extractionThe aqueous layer was extracted with dichloromethane (50 mL×3)
  6. dry with materialThe combined organic layer was dried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was chromatographed on a column of NH-silica gel eluting with ethyl acetate/n-hexane (5:1)

出典と根拠

ORDレコード
ord-071155de79094ed6813b0db9372aa341
出典データセット
uspto-grants-2011_03
特許番号
US07906532B2

反応ノート

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