1-Hydroxybenzotriazole → 4-[6-(4-hydroxy-phenyl)-1-(tetrahydro-pyran-2-yl)-3-vinyl-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 82040

Reaction equation

HRID 82040 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([C:25]([OH:27])=O)[C:11]3[C:16]([CH:17]=[CH2:18])=[N:15][N:14]([CH:19]4[CH2:24][CH2:23][CH2:22][CH2:21][O:20]4)[C:12]=3[N:13]=2)=[CH:4][CH:3]=1.[C:28]([N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1)([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>O1CCCC1.CN(C)C(=O)C>[C:31]([O:30][C:28]([N:35]1[CH2:40][CH2:39][N:38]([C:25]([C:10]2[C:11]3[C:16]([CH:17]=[CH2:18])=[N:15][N:14]([CH:19]4[CH2:24][CH2:23][CH2:22][CH2:21][O:20]4)[C:12]=3[N:13]=[C:8]([C:5]3[CH:4]=[CH:3][C:2]([OH:1])=[CH:7][CH:6]=3)[CH:9]=2)=[O:27])[CH2:37][CH2:36]1)=[O:29])([CH3:34])([CH3:32])[CH3:33]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 143452tert-Butyl piperazine-1-carboxylate2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 1363595036-(4-hydroxy-phenyl)-1-(tetrahydro-pyran-2-yl)-3-vinyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid

Product 1

HCID 1363595044-[6-(4-hydroxy-phenyl)-1-(tetrahydro-pyran-2-yl)-3-vinyl-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-piperazine-1-carboxylic acid tert-butyl esterYield 90%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of 6-(4-hydroxy-phenyl)-1-(tetrahydro-pyran-2-yl)-3-vinyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (3.12 g, 6.62 mmol) in tetrahydrofuran (44 mL) were added 1-boc-piperazine (1.35 g, 7.28 mmol), 1-hydroxybenzotriazole (0.09 g, 0.66 mmol), and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.27 g, 6.62 mmol). After 2 hours, N,N-dimethylacetamide (3 ml), 1-boc-piperazine (0.24 g, 1.32 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.25 g, 1.32 mmol) were added to the reaction mixture. After 1 hour, tetrahydrofuran was evaporated under reduced pressure, water and dichloromethane were then added. The organic layer was washed with an aqueous 1M HCl solution, water, brine, dried (Na2SO4), filtered, concentrated under vacuum. The crude residue was purified on a silica gel column chromatography using a gradient of methanol (0-5%) in dichloromethane to yield the title compound as a yellow foam (3.17 g, 90%).

Workup

  1. waitAfter 1 hour
  2. customtetrahydrofuran was evaporated under reduced pressure, water and dichloromethane
  3. additionwere then added
  4. washThe organic layer was washed with an aqueous 1M HCl solution, water, brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe crude residue was purified on a silica gel column chromatography

Sources & evidence

ORD record
ord-4c715e8bae844704861e9a181c0f1e21
Source dataset
uspto-grants-2014_09
Patent number
US08846712B2

Linked notes

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