Lithium Hydroxide → 4-(tert-Butoxycarbonylamino)-1-(6-(5-(pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yl)piperidine-4-carboxylic acid

HRID 1775043Notes

Reaction equation

HRID 1775043 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1([C:42]([O:44]C)=[O:43])[CH2:14][CH2:13][N:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]3[C:29]4[C:24](=[CH:25][N:26]=[C:27]([C:30]5[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=5)[CH:28]=4)[N:23]([CH:36]4[CH2:41][CH2:40][CH2:39][CH2:38][O:37]4)[N:22]=3)[N:16]=2)[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Li+]>CO.O1CCCC1>[C:1]([O:5][C:6]([NH:8][C:9]1([C:42]([OH:44])=[O:43])[CH2:10][CH2:11][N:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]3[C:29]4[C:24](=[CH:25][N:26]=[C:27]([C:30]5[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=5)[CH:28]=4)[N:23]([CH:36]4[CH2:41][CH2:40][CH2:39][CH2:38][O:37]4)[N:22]=3)[N:16]=2)[CH2:13][CH2:14]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 71253540Methyl 4-(tert-butoxycarbonylamino)-1-(6-(5-(pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yl)piperidine-4-carboxylate

Product 1

HCID 712533374-(tert-Butoxycarbonylamino)-1-(6-(5-(pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yl)piperidine-4-carboxylic acidYield 64.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 240 mg (0.39 mmol) of methyl 4-(tert-butoxycarbonylamino)-1-(6-(5-(pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yl)piperidine-4-carboxylate and 3 ml of 1 M aqueous solution of lithium hydroxide in 20 ml of methanol and 10 ml of tetrahydrofuran was stirred for 18 hours at room temperature and 2 hours at 60° C. The mixture was concentrated in vacuum, neutralized to pH 5 by careful addition of 1 N aqueous HCl and extracted with ethyl acetate. The organic extracts were washed with water, brine, dried over MgSO4 and concentrated to afford 150 mg (43%) of 4-(tert-Butoxycarbonylamino)-1-(6-(5-(pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yl)piperidine-4-carboxylic acid over two steps. ESI MS m/z 600.2 (M+1).

Workup

  1. concentrationThe mixture was concentrated in vacuum
  2. additionneutralized to pH 5 by careful addition of 1 N aqueous HCl
  3. extractionextracted with ethyl acetate
  4. washThe organic extracts were washed with water, brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-0b720c62a51645e9a3e54f139a826de4
Source dataset
uspto-grants-2016_02
Patent number
US09260425B2

Reaction notes

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