5-Chloro-3-nitropyridine-2-carboxaldehyde

2-Amino-3-(6-chloro-3-methoxy-2H-pyrazolo[4, 3-b]pyridin-2-yl)-2-methylpropionitrile (39 mg) was prepared quantitatively using a procedure similar to that described in , part b, except starting from 1-(6-chloro-3-methoxy-2H-pyrazolo[4, 3-.pound.>]pyridin-2-yl)propan-2-one (32 mg). 1-(6-Chloro- 3-methoxy-2/-/-pyrazolo[4, 3-.pound.ι]pyridin-2-yl)propan-2-one was prepared using a procedure similar to that described in Example 105 part a to d except using 5-chloro-3-nitropyridine-2-carboxaldehyde (1.2 g) and decaborane in part a to yield [2-(tert-butyldimethylsilanyloxy)propyl]-(5-chloro-3-nitropyridin-2- yl-methyl)amine (0.4 g, 17percent). 5-Chloro-3-nitropyridine-2-carboxaldehyde was prepared using a procedure similar to that described in Example 136 part a to c except starting from 2-amino-5-chloro- 3-nitropyridine in part a or using commercially available 2-bromo-5-chloro-3-nitropyridine in part b. Alternatively, oxidative cleavage using a 4percent solution of osmium tetroxide in water (2 ml_) and sodium periodate (1.2 g) was carried out in a mixture of THF and water (10:1 , 20 mL) in part c instead of ozonolysis following a procedure similar to that described in Example 61 to afford 5-chloro-3- nitropyridine-2-carboxaldehyde (0.72 g, 72percent) from 5-chloro-3-nitro-2-vinylpyridine (1g).a. To a solution of 2-Amino-3-(6-chloro-3-methoxy-2H-pyrazolo[4, 3-b]pyridin-2-yl)-2-methylpropionitrile (39 mg) was prepared quantitatively using a procedure similar to that described in , part b, except starting from 1-(6-chloro-3-methoxy-2H-pyrazolo[4, 3-£>]pyridin-2-yl)propan-2-one (32 mg). 1-(6-Chloro- 3-methoxy-2/-/-pyrazolo[4, 3-£iota]pyridin-2-yl)propan-2-one was prepared using a procedure similar to that described in Example 105 part a to d except using 2-Amino-3-(6-chloro-3-methoxy-2H-pyrazolo[4, 3-b]pyridin-2-yl)-2-methylpropionitrile (39 mg) was prepared quantitatively using a procedure similar to that described in , part b, except starting from 1-(6-chloro-3-methoxy-2H-pyrazolo[4, 3-£>]pyridin-2-yl)propan-2-one (32 mg). 1-(6-Chloro- 3-methoxy-2/-/-pyrazolo[4, 3-£iota]pyridin-2-yl)propan-2-one was prepared using a procedure similar to that described in Example 105 part a to d except using To a solution of delta-chloro-S-nitropyridine^-carboxaldehyde (1 g), described in Example 146, in 1 , 2-dichloroethane (20 mL) was added 4A molecular sieves powder and 2-(tert-butyldimethylsilanyloxy)propylamine (1.22 g) described in Example 105 part a. After stirring overnight at room temperature, sodium cyanoborohydride (0.4 g) and acetic acid (0.33 mL) were added at O0C. After stirring for one hour at O0C, the reaction mixture was heated to 65C overnight. The reaction mixture was filtered through a plug of Celite and concentrated under reduced pressure to yield a residue that was purified by chromatography (SiO2, heptane/EA) to afford 2-[2-(tert- butyldimethylsilanyloxy)propyl]-6-chloro-2/-/-pyrazolo[4, 3-iotab]pyridine (0.6 g, 37%). MS(ES): M/Z [M+H]=326. 1 H NMR: (400 MHz, CHLOROFORM-d): -0.37 (s, 3H), -0.09 (s, 3H), 0.79 (s, 9H), 1.24 (d, J=6.1 Hz, 3H), 4.21 - 4.31 (m, 1 H), 4.33 - 4.38 (m, 1 H), 4.40 - 4.47 (m, 1 H), 8.00 (dd, J=2.1 , 0.9 Hz, 1H), 8.22 (d, J=O.7 Hz, 1H) and 8.48 (d, J=2.1 Hz, 1 H).

Molecular Weight:186.55
XLogP3:1.1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:185.9832197
Monoisotopic Mass:185.9832197
Topological Polar Surface Area:75.8
Heavy Atom Count:12
Complexity:194
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes