Hydrochloric Acid → 2-(3-(6-(4-(tertButoxycarbonyl)piperazin-1-yl)pyridin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)acetic acid

HRID 1775064Notes

Reaction equation

HRID 1775064 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:19]=[C:18]([C:20]3[C:28]4[C:23](=[CH:24][N:25]=[C:26]([CH:29](C(OCC)=O)[C:30]([O:32]CC)=[O:31])[CH:27]=4)[N:22]([CH:40]4[CH2:45][CH2:44][CH2:43][CH2:42][O:41]4)[N:21]=3)[CH:17]=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li+].[OH-].Cl>CO.C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14]2[N:19]=[C:18]([C:20]3[C:28]4[C:23](=[CH:24][N:25]=[C:26]([CH2:29][C:30]([OH:32])=[O:31])[CH:27]=4)[N:22]([CH:40]4[CH2:45][CH2:44][CH2:43][CH2:42][O:41]4)[N:21]=3)[CH:17]=[CH:16][CH:15]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 71253905Diethyl 2-(3-(6-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)malonate

Product 1

HCID 712534252-(3-(6-(4-(tertButoxycarbonyl)piperazin-1-yl)pyridin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)acetic acid

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of diethyl 2-(3-(6-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)malonate (117 mg (0.188 mmol) and 0.5 ml of 1 M aqueous solution of LiOH in 6 ml of methanol/THF mixture (2:1) was heated at 60° C. for 1 hour. The mixture was acidified with 1 N aqueous HCl to pH<1 and stirred for 20 min. The mixture was concentrated, the residue partitioned between ethyl acetate and water. The pH of the mixture was adjusted to 4 by careful addition of saturated aqueous sodium bicarbonate. The organic extracts were washed with brine, dried over MgSO4 and concentrated to afford 2-(3-(6-(4-(tertButoxycarbonyl)piperazin-1-yl)pyridin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)acetic acid (68 mg, 32% over two steps. ESI MS m/z 523.4 (M+1).

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue partitioned between ethyl acetate and water
  3. additionThe pH of the mixture was adjusted to 4 by careful addition of saturated aqueous sodium bicarbonate
  4. washThe organic extracts were washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-36ec7bfa61b94dc8bae391bc2c95368d
Source dataset
uspto-grants-2016_02
Patent number
US09260425B2

Reaction notes

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