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

HRID 82024Notes

Reaction equation

HRID 82024 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:26]([OH:28])=O)[C:5]2[C:10](/[CH:11]=[CH:12]/[C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=3)=[N:9][N:8]([CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][O:21]3)[C:6]=2[N:7]=1.[C:29]([N:36]1[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]1)([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C)C(=O)C.O1CCCC1>[C:32]([O:31][C:29]([N:36]1[CH2:41][CH2:40][N:39]([C:26]([C:4]2[C:5]3[C:10](/[CH:11]=[CH:12]/[C:13]4[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=4)=[N:9][N:8]([CH:20]4[CH2:25][CH2:24][CH2:23][CH2:22][O:21]4)[C:6]=3[N:7]=[C:2]([Cl:1])[CH:3]=2)=[O:28])[CH2:38][CH2:37]1)=[O:30])([CH3:35])([CH3:33])[CH3:34]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 143452tert-Butyl piperazine-1-carboxylateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86678161HCID 86678161, compound

Product 1

HCID 866781604-[6-chloro-3-[(E)-2-(4-chloro-phenyl)-vinyl]-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carbonyl]-piperazine-1-carboxylic acid tert-butyl esterYield 54%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of 6-chloro-3-[(E)-2-(4-chloro-phenyl)-vinyl]-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (2 g, 4.79 mmol) in a mixture of anhydrous tetrahydrofuran (42 ml) and N,N-dimethylacetamide (10 ml) were added 1-boc-piperazine (0.98 g, 5.27 mmol), 1-hydroxybenzotriazole (0.06 g, 0.48 mmol), and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.91 g, 4.79 mmol). The reaction mixture was stirred at room temperature for 4 hours, tetrahydrofuran was evaporated under reduced pressure, water and dichloromethane were then added. The organic phase was separated, dried over anhydrous sodium sulfate, filtered and concentrated in vacuum. The crude residue was purified on a silica gel column chromatography using a gradient of ethyl acetate (0-45%) in cyclohexane to yield the title compound as a yellow foam (1.51 g, 54%).

Workup

  1. customtetrahydrofuran was evaporated under reduced pressure, water and dichloromethane
  2. additionwere then added
  3. customThe organic phase was separated
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuum
  7. customThe crude residue was purified on a silica gel column chromatography

Sources & evidence

ORD record
ord-16aee1fdb6e24b319aa6129748e739f0
Source dataset
uspto-grants-2014_09
Patent number
US08846712B2

Reaction notes

Loading…