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Preparation of 5-(4-Ethyl-piperazin-1-ylmethyl)-pyridin-2-ylamine Disclosure Number: IPCOM000250211D
Publication Date: 2017-Jun-12
Document File: 1 page(s) / 80K

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Preparation of 5-(4-Ethyl-piperazin-1-ylmethyl)-pyridin-2-ylamine

5-(4-Ethyl-piperazin-1-ylmethyl)-pyridin-2-ylamine (referred to as Compound A) is

an intermediate of N-{5-[(4-ethyl-1-piperazinyl)methyl]-2-pyridinyl}-5-fluoro-4-(4-fluoro-1-

isopropyl-2-methyl-1H-benzimidazol-6-yl)-2-pyrimidinamine (referred to as Compound 1)

Disclosed herein is a process for preparing Compound A from 1-(6-bromo-pyridin-3-


Benzamide (47.1 mg; 0.39 mmol), Cesium carbonate (173 mg; 0.53 mmol) and a

Palladium catalyst were mixed together, the Schlenk tube was evacuated and back-filled with

argon (several times), solution of 1-(6-bromo-pyridin-3-ylmethyl)-4-ethyl-piperazine (100

mg; 0.35 mmol) in DME (aps.; 1 ml; deaerated) was added.

Reaction mixture stirred at 50°C for 24 hours. Solvent was evaporated to reduced volume

(app. 90%) and water was added (2 ml), reaction mixture extracted with EtAc (2x2 ml),

washed with brine, dried (Na2SO4) and evaporated to dryness, 128 mg of crude (94% pure)

was obtained in form of thick oil.

Crude product dissolved in DCM (3 ml) and stirred overnight. Reaction mixture filtered off

and evaporated to dryness. Residue (115 mg) was used in hydrolysis step.

Fore mentioned crude amide dissolved in MeOH (1.15 ml), 2M NaOH (0.575 ml) was

added and reaction mixture stirred at 100°C for 30 minutes, most of the MeOH was

evaporated at vacuum, 6M HCl was added and pH adjusted at 1-2, water was added (2 ml)

and extracted with DCM (3x2 ml), water...