4-(5-AMINOPYRIDIN-2-YL)PIPERAZINE-1-CARBOXYLIC ACID TERT-BUTYL ESTER

2-Bromo-5-nitro-pyridine (11.39 g, 56.1 mmol), tetrabutylammonium iodide (TBAI) (1.04 g, 0.05 mmol), potassium carbonate (8.53 g, 61.7 mmol) and piperazine-1-carboxylic acid tert-butyl ester (11.5 g, 61.7 mmol) were mixed together in DMSO (100 mL) and gently warmed to 50 C. for 3 hours and cooled to room temperature overnight. The reaction was diluted with EtOAc (200 mL), the salts were filtered and then the EtOAc was evaporated to leave the DMSO solution. This was diluted with water and a precipitate formed. This precipitate was filtered, washed with water, and then dried in an oven vacuum to give 4-(5-nitro-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester (16.1 g, 93percent) as a light orange solid. Place 4-(5-nitro-pyridin-2-yl)-piperazine-l-carboxylic acid tert-butyl ester (1.14 g, 3.70 mmol) in 1:1 EtOAc:MeOH (20 mL). Add 10percent Pd on carbon using EtOAc (5 mL). Purge the reaction and then add hydrogen. Repeat the purge/fill cycle twice, and place the reaction under a balloon of hydrogen and stir at room temperature for 20 hours. Filter the reaction through a pad of Celite.(R). and wash the filter cake with EtOAc. Collect the filtrate and concentrate under reduced pressure to yield 1.01 g (98percent) of the title compound. MS(ES): m/z = 279 [M+H].Example 197b (General flow chemistry reduction method). Using 10percent Pd/C as catalyst, a solution of compound 3b (1 mmol, 208 mg) in a 1:1 mixture of ethyl acetate: ethanol (30 mL) was pumped though the H-Cube.(TM).. The pressure of the system was set to 1 bar, and the temperature to 70 °C. After 30 minutes, all the reaction mixture had passed though the HCube.(TM).. The fraction was analyzed using TLC, which showed complete conversion of the product, and the solvent was reduced to dryness, affording a dark red oil 171 mg (96percent) yield. The CatCart.(TM). was then washed with ethanol for approximately 10 minutes and the washings were discarded.A suspension of 4-(5-nitro-pyridin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester (10.8 g) obtained in Example (38a) and 10percent palladium-carbon catalyst (2.15 g) in ethanol (300 mL) was stirred at room temperature under a hydrogen atmosphere for five hours. The reaction mixture was filtered and concentrated. The residue was vigorously stirred in isopropyl ether, collected by filtration and dried under reduced pressure, and 6.59 g (68percent) of the title compound was obtained as a pale pink solid. MS(FAB) m/z:279 (M + H)

Molecular Weight:278.35
XLogP3:1.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:3
Exact Mass:278.17427596
Monoisotopic Mass:278.17427596
Topological Polar Surface Area:71.7
Heavy Atom Count:20
Complexity:335
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes