Hydrochloric Acid → 3-[({[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]benzoic Acid

HRID 564533Notes

Reaction equation

HRID 564533 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:33][CH3:34])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[CH:24]=[C:25]([CH:30]=[CH:31][CH:32]=3)[C:26]([O:28]C)=[O:27])=[O:22])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2].[Li+].[OH-].O.Cl>[Cl-].[Na+].O.C(Cl)Cl.CO>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:33][CH3:34])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[CH:24]=[C:25]([CH:30]=[CH:31][CH:32]=3)[C:26]([OH:28])=[O:27])=[O:22])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 3939Lithium HydroxideHCID 57813262Methyl 3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]benzoate

Product 1

HCID 578132773-[({[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]benzoic AcidYield 93.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A mixture of methyl 3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]benzoate (8.52 g, 18.3 mmol), LiOH (3.84 g, 91.5 mmol), water (30 mL) and methanol (60 mL) was stirred at room temperature overnight. The aqueous layer was acidified with 2 N HCl to pH around 1. Brine (30 mL) was added to the solution. White solid was precipitated out from the solution. The solid was filtered off and washed with water. The aqueous layer was extracted with ethyl acetate twice. The combined organic layers were concentrated under vacuum to give a solid. All solid was dissolved in DCM and combined into one batch. Solvent was concentrated to give crude residue. The crude residue was then triturated with ether to give 3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]benzoic acid as a white solid (7.72 g, 86%). LC-MS m/z 452 (M+H)+.

Workup

  1. customWhite solid was precipitated out from the solution
  2. filtrationThe solid was filtered off
  3. washwashed with water
  4. extractionThe aqueous layer was extracted with ethyl acetate twice
  5. concentrationThe combined organic layers were concentrated under vacuum
  6. customto give a solid
  7. concentrationSolvent was concentrated
  8. customto give crude residue
  9. customThe crude residue was then triturated with ether

Sources & evidence

ORD record
ord-e94aba25e0224e6eaa622f0c929ab38a
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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