4-[[(1,1-Dimethylethoxy)carbonyl]amino]-3-pyridinecarboxylic acid

4-tert-Butoxycarbonylamino-nicotinic acicL To a solution of 4-tert- butoxycarbonylamino-nicotinic acid methyl ester (6.02g, 23.86 mmol) in dioxane (100 mL) was added aq. sodium hydroxide (0.970 N solution, 28.05 mL, 27.20 mmol). The solution was heated to 6OIntermediate 6AH: 4- fcr To a stirred solution of 4-aminopyridine-3-carboxylic acid (1.0 g, 7.2 mmol), Boc anhydride in THF:water (1:1, 20 mL) was added DMAP and stirred for 3 h at room temperature. To this was added ethyl acetate (25 mL) and water (25 mL). Aqueous layer was separated, extracted with ethyl acetate (25 mL). Combined organic layer was washed with brine (25 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to furnish 1.2 g (69percent) of 4-(tert-butoxycarbonylamino)pyridine-3-carboxylic acid. [0349] MS (ES) m/z 239.1 (M+1)To a stirred solution of BL (12 g, 0.06 mol) in dry THF (200 mL) under inert atmosphere was added n-butyl lithium (79.12 mL, 0.18 mol) at -78 °C. The reaction was warmed to 0 °C and stirred for 30 min. Carbon dioxide gas was added to the reaction mass at -78 °C for 1 h, then at RT for 1 h. The reaction was monitored by TLC. After complete consumption of the starting material, the reaction mass was diluted with water (200 mL) and washed with diethyl ether (2x150 mL). The aqueous layer was acidified with citric acid to pH~4. The obtained solid was filtered and dried under vacuum to afford BM (5.1 g, 35percent) as a white solid. *H NMR (400 MHz, DMSO-i: δ 11.76 (br s, 1H), 8.96 (s, 1H), 8.52 (d, / = 15.0 Hz, 1H), 8.22 (d, / = 15.0 Hz, 1H), 1.49 (s, 9H).-Buli (1.6 M soln, 155 mL, 249 mmol) was added to a stirred solution of TMEDA (37.36 mL, 249 mmol) in THF AT-40 °C. The solution was allowed to come at room temperature over 10 min and stirred for another 10 min. The solution was cooled TO-78 °C. A solution OF PYRIDINE-4-YL-CARBAMIC acid-tert-butyl ester (117) (22 g, 113.26 mmol) in THF was added slowly. The solution was allowed to come at room temperature within 3 h. After stirring at room temperature for 15 min the solution was again cooled to -78 OC and a freshly crushed dry ice was added. The solution was allowed to come at room temperature, stirred for 30 min and poured into ice cold 10 percent NH4C1 solution. The solution was basified by IN NaOH solution and washed by dichloromethane. The pH of aqueous phase was adjusted to 4 by cold 10 percent HC1 solution. The solids formed were filtered, washed by water and dried under vacuum at room temperature to yield 16.3 g (30 percent) 4-tert-butoxycarbonylamino-nicotinic acid (118) as white solids. MP: 260 °C ; 1H- NMR (DMSO-d6): d 1.49 (s, 9H), 8.23 (d, J= 6.0 Hz, 1H), 8.55 (D, J= 6.0 Hz, 1H), 8. 96 (s, 1H); EIMS M/Z 238 (M+1).To a stirring solution of4- (Boc-amino) pyridine (1.027 g, 5.30 mmol) in THF at-36 C (internal temperature) was added a 1.7 M solution of t-butyl lithium in pentane (6.5 mL, 11 mmol), and the rate of addition was controlled so as to keep the internal temperature below-28 C. After an additional hour (temperature kept between-30 C and- 50 C) carbon dioxide (g) was bubbled through the solution and the cold bath was removed. After about 15 min, the mixture was poured into ice water and the aqueous phase was washed with dichloromethane. The pH was adjusted to 4-5 with citric acid, and the resulting precipitate was washed with dichloromethane and methanol and dried in vacuo to give the title compound (0.811 g, 64percent) as an off-white solid. 1NMR IS-MS, m/e239. 0 (m+l) Analysis forCllH14N2 4 : Calcd: C, 55.46 ; H, 5.92 ; N, 11.76 ; Found: C, 55.73 ; H, 6.07 ; N, 11.75.B. 4-tert-Butoxycarbonylamino-nicotinic acicL To a solution of 4-tert- butoxycarbonylamino-nicotinic acid methyl ester (6.02g, 23.86 mmol) in dioxane (100 mL) was added aq. sodium hydroxide (0.970 N solution, 28.05 mL, 27.20 mmol). The solution was heated to 6OIntermediate 6AH: 4- fcr To a stirred solution of 4-aminopyridine-3-carboxylic acid (1.0 g, 7.2 mmol), Boc anhydride in THF:water (1:1, 20 mL) was added DMAP and stirred for 3 h at room temperature. To this was added ethyl acetate (25 mL) and water (25 mL). Aqueous layer was separated, extracted with ethyl acetate (25 mL). Combined organic layer was washed with brine (25 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to furnish 1.2 g (69percent) of 4-(tert-butoxycarbonylamino)pyridine-3-carboxylic acid. [0349] MS (ES) m/z 239.1 (M+1)To a stirred solution of BL (12 g, 0.06 mol) in dry THF (200 mL) under inert atmosphere was added n-butyl lithium (79.12 mL, 0.18 mol) at -78 °C. The reaction was warmed to 0 °C and stirred for 30 min. Carbon dioxide gas was added to the reaction mass at -78 °C for 1 h, then at RT for 1 h. The reaction was monitored by TLC. After complete consumption of the starting material, the reaction mass was diluted with water (200 mL) and washed with diethyl ether (2x150 mL). The aqueous layer was acidified with citric acid to pH~4. The obtained solid was filtered and dried under vacuum to afford BM (5.1 g, 35percent) as a white solid. *H NMR (400 MHz, DMSO-i: δ 11.76 (br s, 1H), 8.96 (s, 1H), 8.52 (d, / = 15.0 Hz, 1H), 8.22 (d, / = 15.0 Hz, 1H), 1.49 (s, 9H).-Buli (1.6 M soln, 155 mL, 249 mmol) was added to a stirred solution of TMEDA (37.36 mL, 249 mmol) in THF AT-40 °C. The solution was allowed to come at room temperature over 10 min and stirred for another 10 min. The solution was cooled TO-78 °C. A solution OF PYRIDINE-4-YL-CARBAMIC acid-tert-butyl ester (117) (22 g, 113.26 mmol) in THF was added slowly. The solution was allowed to come at room temperature within 3 h. After stirring at room temperature for 15 min the solution was again cooled to -78 OC and a freshly crushed dry ice was added. The solution was allowed to come at room temperature, stirred for 30 min and poured into ice cold 10 percent NH4C1 solution. The solution was basified by IN NaOH solution and washed by dichloromethane. The pH of aqueous phase was adjusted to 4 by cold 10 percent HC1 solution. The solids formed were filtered, washed by water and dried under vacuum at room temperature to yield 16.3 g (30 percent) 4-tert-butoxycarbonylamino-nicotinic acid (118) as white solids. MP: 260 °C ; 1H- NMR (DMSO-d6): d 1.49 (s, 9H), 8.23 (d, J= 6.0 Hz, 1H), 8.55 (D, J= 6.0 Hz, 1H), 8. 96 (s, 1H); EIMS M/Z 238 (M+1).To a stirring solution of4- (Boc-amino) pyridine (1.027 g, 5.30 mmol) in THF at-36 C (internal temperature) was added a 1.7 M solution of t-butyl lithium in pentane (6.5 mL, 11 mmol), and the rate of addition was controlled so as to keep the internal temperature below-28 C. After an additional hour (temperature kept between-30 C and- 50 C) carbon dioxide (g) was bubbled through the solution and the cold bath was removed. After about 15 min, the mixture was poured into ice water and the aqueous phase was washed with dichloromethane. The pH was adjusted to 4-5 with citric acid, and the resulting precipitate was washed with dichloromethane and methanol and dried in vacuo to give the title compound (0.811 g, 64percent) as an off-white solid. 1NMR IS-MS, m/e239. 0 (m+l) Analysis forCllH14N2 4 : Calcd: C, 55.46 ; H, 5.92 ; N, 11.76 ; Found: C, 55.73 ; H, 6.07 ; N, 11.75.B.

Molecular Weight:238.24
XLogP3:1.5
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:4
Exact Mass:238.09535693
Monoisotopic Mass:238.09535693
Topological Polar Surface Area:88.5
Heavy Atom Count:17
Complexity:298
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes