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

HRID 602461Notes

Reaction equation

HRID 602461 reaction equation
[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

Participants

4

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-071155de79094ed6813b0db9372aa341
Source dataset
uspto-grants-2011_03
Patent number
US07906532B2

Reaction notes

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