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

HRID 602456Notes

Reaction equation

HRID 602456 reaction equation
[OH:1][C:2]1([CH2:8][C@H:9]2[CH2:14][CH2:13][C@@H:12]([NH:15][C:16]([C:18]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]([CH:27]([CH3:29])[CH3:28])[N:19]=3)=[O:17])[CH2:11][N:10]2C(OC(C)(C)C)=O)[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1.Cl>CO>[OH:1][C:2]1([CH2:8][C@H:9]2[NH:10][CH2:11][C@@H:12]([NH:15][C:16]([C:18]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]([CH:27]([CH3:29])[CH3:28])[N:19]=3)=[O:17])[CH2:13][CH2:14]2)[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 67270163tert-Butyl cis-2-[(4-hydroxytetrahydro-2H-pyran-4-yl)methyl]-5-{[(1-isopropyl-1H-indazol-3-yl)carbonyl]amino}piperidine-1-carboxylate

Product 1

HCID 67270191N-{cis-6-[(4-Hydroxytetrahydro-2H-pyran-4-yl)methyl]piperidin-3-yl}-1-isopropyl-1H-indazole-3-carboxamideYield 106.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The mixture of tert-butyl cis-2-[(4-hydroxytetrahydro-2H-pyran-4-yl)methyl]-5-{[(1-isopropyl-1H-indazol-3-yl)carbonyl]amino}piperidine-1-carboxylate (292 mg, 0.583 mmol, step 6 of Example 2) and 10% hydrochloric acid in methanol (3 mL) was stirred at room temperature for 20 h. The mixture was concentrated under reduced pressure and the resulting residue was dissolved in dichloromethane/methanol (10/1, 10 mL). The solution was filtered through amine-silica gel washing with dichloromethane/methanol (10/1, 200 mL). The filtrate was concentrated under reduced pressure and the resulting residue was chromatographed on a column of silica gel eluting with dichloromethane/methanol/25% ammonium hydroxide (10:1:0.2) to give 249 mg (99%) of the title compound as a white crystal.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. dissolutionthe resulting residue was dissolved in dichloromethane/methanol (10/1, 10 mL)
  3. filtrationThe solution was filtered through amine-silica gel washing with dichloromethane/methanol (10/1, 200 mL)
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customthe resulting residue was chromatographed on a column of silica gel eluting with dichloromethane/methanol/25% ammonium hydroxide (10:1:0.2)

Sources & evidence

ORD record
ord-66b27315a6614e72b96ac1613b645e30
Source dataset
uspto-grants-2011_03
Patent number
US07906532B2

Reaction notes

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