5-Amino-2-chloroisonicotinic acid

Brown powder

5-Amino-2-chloropyridine-4-carboxylic acid. Step (d): 5-AMINO-2-CHLORO-ISONICOTINIC acid A suspension of 5-tert-butoxycarbonylamino-2-chloro-isonicotinic acid in methylene chloride (600mL) was treated dropwise at room temperature with TFA until the solid had dissolved into solution (95 mL). The reaction mixture was stirred overnight under nitrogen at room temperature, evaporated to dryness, diluted with water, and the solid collected by filtration. The solid was washed with water, dried under low heat and house vacuum, to afford 19.55g of 5-amino- 2-chloro-isonicotinic acid as a yellow solid (93.6percent yield). 1H NMR (400 MHz, DMSO-D6) 8 ppm 7.5 (s, 2H), 8.0 (s, 2H) MS (APCI) M+1= 173.0; Step (d): 5-AMINO-2-CHLORO-ISONICOTINIC acid A 3 L round bottomed flask was charged with 5-tert- BUTOXYCARBONYLAMINO-2-CHLORO-ISONICOTINIC acid (138 g, 0.51 moles), 1 L of CH2C12, and 400 mL of TFA. The resulting orange solution was stirred overnight at room temperature. One liter of H20 was added to the reaction solution, which caused a solid to precipitate out. The solid was collected, washed once with H2O and dried overnight in the vacuum oven at 45°C. The reaction yielded 69.6 g (80percent total yield) of 5-amino-2-chloro-isonicotinic acid as a pale yellow solid, which was pure enough by NMR to use in the next reaction. ON (DMSO) 7.99 (1 H, d), 7.45 (1 H, d) MS [M+H] + 173Step (e) 6-Chloro-3H-pyrido [3, 4-d] pyrimidin-4-one A 1 L round bottomed flask was charged with 5-amino-2-chloro- isonicotinic acid (69.5 g, 0.40 moles), formamidine acetate (84 g, 0.81 moles, 2 mole equivalents), and 600 mL of methoxyethanol. The resulting solution was heated at reflux for 18 hours. After cooling to 5°C, a precipitate was collected by filtration, washed twice with methoxyethanol, and dried overnight in the vacuum oven at 45°C. The reaction yielded 67 g (92percent total yield) of 6-chloro-3H- pyrido [3, 4-D] PYRIMIDIN-4-ONE as a tan solid that was sufficiently pure by NMR to use in the next reaction. 8H (DMSO) 12.70 (1 H, s), 8.86 (1 H, d), 8. 19 (1 H, s), 7.93 (1 H, d) MS [M+H3+ 182 (4.0 g, 23 mmol) was added to SOCl2 (50 mL), the mixture was heated to 80 C. for 4 h. After the reaction was completed, the mixture was cooled to room temperature and concentrated. The residue was dissolved in anhydrous THF (20 mL), and then the mixture was cooled under ice water bath, a concentrated aqueous ammonia (100 mL) was added. The reaction was completed, and the mixture was extracted for five times with CH2Cl2 (100 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtrated and concentrated to obtain compound 5-amino-2-chloroisonicotinamide (3.5 g, yield: 88%).

Molecular Weight:172.57
XLogP3:1.2
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:172.0039551
Monoisotopic Mass:172.0039551
Topological Polar Surface Area:76.2
Heavy Atom Count:11
Complexity:165
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes