5-Amino-2-chloropyridine

Light yellow to brown crystalline powder

General procedure: The nitro compound (1 equiv), HFIP (10 equiv), Fe powder (5 equiv) were mixed in a tube. Then 2 N HCl aqueous solutions was added to the reaction mixture. After stirring at room temperature for 30 min, the reaction mixture was neutralized with sat. NaHCO[Referential Example 7] 1-(5-Methoxy-2-pyridyl)-5-phenyl-1H-pyrazole-3-carboxylic acid; [Show Image] 1) 5-Amino-2-chloropyridine; Conc. hydrochloric acid (1 ml) was added to a solution of 2-chloro-5-nitropyridine (20 g) in a mixture of ethanol (160 ml) and water (40 ml). Iron which was reduced by hydrogen (70.5 g) was added in several potions to this mixture at room temperature and the mixture was stirred at 90°C for 1 hour. After cooling with air, the reaction liquid was filtered through celite, and the solvent was evaporated under reduced pressure. The residue was purified by chromatography on silica gel (ethyl acetate-hexane) to give the amine derivative (15.2 g, 94percent) as a solid. COMPOUND 4- [6- (4-METHOXY-BENZYLCARBAMOYL)-4-OXO-4H-PYRIDO [3, 4-d] pyrimidin-3- ylmethyl]-benzoic acid Preparation Method 1: Step (a): 6-CHLORO-PYRIDIN-3-YLAMINE A solution of 2-chloro-5-nitropyridine (50. 00g, 315. 5MMOL) in THF (400mL) was treated with Ra Ni (8. 0G), and the reaction mixture was hydrogenated at 56 psi of hydrogen at 100°C for 20 hours. The reaction mixture was cooled to room temperature and filtered. The filtrate was evaporated, and the resulting solid was triturated with hexanes/ethyl acetate 9: 1. The solids were collected by filtration and dried to give 37. 61G of 6-CHLORO-PYRIDIN-3-YLAMINE as a brown solid (92.8percent yield). 1H NMR (400 MHz, CHLOROFORM-D) d ppm 3.7 (s, 2H), 6.9 (m, 1H), 7.1 (d, J=9. OHz, 1H), 7.8 (s, 1H) MS (APCI) M+l = 129.0; Preparation Method 2 : It should be appreciated that the starting material and intermediates described above in Preparation Method 1 are also used below in Preparation Method 2. However, reagents, reaction times and temperatures, work-ups, purifications, and the like may differ between Preparation Methods 1 and 2. Step (a): Preparation of 6-chloro-pyridin-3-ylamine A 5 gallon stirred stainless steel pressure reactor was charged with 2-chloro-5- nitropyrimidine (571.8 g, 3.61 moles), 8.5 L of THF, and Raney Nickel (150 g). The vessel was pressurized to 50 psi with hydrogen gas, and the mixture was stirred at room temperature overnight. An aliquot checked by mass spectrometry showed the reaction was complete. The solvent was reduced to about 750 mL and left sitting at room temperature overnight. A first crop of solid had formed in the about 750 mL of solvent remaining. The solid was collected by filtration, and the filtercake was washed 1 time with THF, 2 times with heptane, and dried overnight in a vacuum oven at 45°C. Separately, about 1.5 L of heptane were added to the filtrate from above, and the mixture was refrigerated for 2 hours. A second crop of solids that formed were collected by filtration, and the filtercake was washed 1 time with heptane and dried overnight in the vacuum oven at 45°C. Meanwhile, the filtrate from the second crop was rotary evaporated, and a residual solid third crop was collected and dried overnight in the vacuum oven at 45°C. The reaction yielded 432 g (93percent total yield in 3 crops) of 6-chloro-pyridin- 3-ylamine that was sufficiently pure by NMR to carry on in the next reaction without further purification. OH (DMSO) 7.64 (1 H, M), 7.03 (1 H, d), 6.93 (1 H, d), 5.44 (2 H, s)a) Preparation of 6-chloro-pyridin-3-ylamine 2-Chloro-5-nitro-pyridine (15 g, 94.9 mmol) was hydrogenated over Raney nickel (2 g) in methanol (200 mL) at 70 psi and r.t. for 26 h. The mixture was filtered through Celite and concentrated to afford 6-chloro-pyridin-3-ylamine (10.4 g, 83percent).Step 1.

Molecular Weight:128.56
XLogP3:1.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:128.0141259
Monoisotopic Mass:128.0141259
Topological Polar Surface Area:38.9
Heavy Atom Count:8
Complexity:76.8
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes