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

HRID 602461노트

반응식

HRID 602461 반응식
[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

참가 물질

4

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-071155de79094ed6813b0db9372aa341
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07906532B2

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