1H-Pyrazolo[3,4-c]pyridine

To a solution of XI (150 mg, 0.339 mmol) in acetone (2 mL) was added 2H-pyrazolo [3, 4- c]pyridine (60.5 mg, 0.508 mmol) and K2C03 (92.8 mg, 0.678 mmol). After stirring at 15C for 16 hrs, the reaction mixture was treated with water (5 mL) and extracted with EtOAc (2 x 10 mL). The combined organic layer was washed with brine (5 mL). The organic layer was dried over Na2SC>4, filtered and concentrated. The residue was purified by HPLC (column: Waters Xbridge 150*25 5u), water (lOmM NH4HC03)-ACN, gradient: 45-65% B, flow rate: 25 mL/min)) to give Compound 55 (20 mg, 12%) as a solid and Compound 54 (15 mg, impure) as a solid, which was combined with another batch prepared from 50 mg of XI. The impure sample was further purified by prep-TLC (PE/EtOAc = 1/1) to give Compuond 54 (8 mg) as a solid. (0813) Compound 54: (0814) 1H NMR (400 MHz, CDC13) delta 9.40-9.20 (m, 1H), 8.25-8.10 (m, 1H), 8.10-8.00 (m, 1H), 7.70- 7.55 (m, 1H), 5.39-5.12 (m, 2H), 3.63-3.10 (m, 1H), 3.52-3.48 (m, 1H), 3.42 (s, 3H), 2.34-2.01 (m, 3H), 2.00-1.62 (m, 10H), 1.62-1.48 (m, 5H), 1.48-0.97 (m, 6H), 0.82 -0.63 (m, 6H). (0815) LCMS Rt = 0.766 min in 2 min chromatography, 30-90AB_2MIN_E, purity 100%, MS ESI calcd. for C29H42N3O3 [M+H]+ 480 found 480. (0816) Compound 55: (0817) 1H NMR (400 MHz, CDCI3) delta 8.81-8.78 (m, 1H), 8.36-8.32 (m, 1H), 8.08 (s, 1H), 7.65-7.61 (m, 1H), 5.28-5.12 (m, 2H), 3.70-3.60 (m, 1H), 3.52-3.48 (m, 1H), 3.41 (s, 3H), 2.21-2.01 (m, 2H), 1.84-1.65 (m, 4H), 1.65-1.48 (m, 6H), 1.48-1.19 (m, 10H), 1.19-0.98 (m, 2H), 0.82 -0.70 (m, 6H). (0818) LCMS Rt = 0.793 min in 2 min chromatography, 30-90AB_2MIN_E, purity 100%, MS ESI calcd. for C29H42N3O3 [M+H]+ 480 found 480.To a suspension of 2H-pyrazolo[3, 4-c]py (125 mg, 1.05 mmol) and K2CO3 (193 mg, 1.40 mmol) in acetone (10 mL) was added Jl (300 mg, 0.701 mmol) at 15C under N2. The mixture was stirred at 15C for 16 hrs. The mixture was filtered and concentrated to give a solid, which was purified by pre-HPLC (Column:Xtimate C18 150*25mm*5um; Condition: water(0.05%HCl)-ACN; Gradient 16%-41%B; Gradient Time(min):9.5) to afford Compound 27 (8.00 mg, 2% ) as a solid and Compound 28 (6.00 mg, 2%) as a solid. (0620) Compound 27: 1H NMR (400 MHz, CDC13) delta 9.25 (s, 1H), 8.19-8.14 (m, 1H), 7.98 (s, 1H), 7.55-7.50 (m, 1H), 5.36-5.20 (m, 2H), 3.87-3.85 (m, 1H), 2.75-2.70 (m, 1H), 2.33-1.72 (m, 5H), 1.50-1.12 (m, 19H), 0.90-0.77 (m, 4H), 0.71 (s, 3H). LCMS Rt = 0.725 min in 1.5 min chromatography, 5-95 AB, purity 100 %, MS ESI calcd. for C28H40N3O3 [M+H]+ 466, found 466. (0621) Compound 28: (0622) 1H NMR (400 MHz, CDC13) delta 8.80 (s, 1H), 8.36-8.32 (m, 1H), 8.09 (s, 1H), 7.65-7.60 (m, 1H), 5.32-5.20 (m, 2H), 3.87-3.85 (m, 1H), 2.75-2.68 (m, 1H), 2.33-1.68 (m, 7H), 1.50-1.18 (m, 18H), 0.77 (s, 3H), 0.72 (s, 3H). (0623) LCMS Rt = 0.748 min in 1.5 min chromatography, 5-95 AB, purity 100 %, MS ESI calcd. for C28H40N3O3 [M+H]+ 466, found 466.To a solution of 2-chloro-N-(2 , 4-d imethoxybenzyl)-5-n itrobenzenesulfonamide (700 mg, 1.81 mmol) in acetonitrile (18 mL) were added 1H-To a solution of pyrazolo[3.4-c]pyridine (2.56 g, 21.5 mmol) in DMF (60 mL) is added NaH (60% in mineral oil, 1.03 g, 25.78 mmol) portionwise at 0 C. After stirring at 0 C for 30 min.2, 4-dichloropyrimidine (3.20 g, 21.5 mmol) is added, and the mixture is allowed to stir at 15 C for 12 hrs. The resulting mixture is quenched with water (200 mL) and the mixture is extracted with EtOAc (100 mL x 3), and washed with water (100 mL x 4), dried with Na2SO4 and concentrated in vacuo. The residue is purified by silica gel chromatography (petroleum ether: EtOAc =10:1), to give 2-chloro-4-(pyrazolo[3.4-c]pyrid-1-ylpyrimidine.To a solution of To a suspension of K2CO3(55mg, 0.4mmol) in THF (5mL) was added To a mixture of I-AI (200 mg, 0.47 mmol) and K2C03 (129 mg, 0.94 mmol) in acetone (5 mL) was added lH-pyrazolo[3, 4-c]pyridine (83.9 mg, 0.705 mmol) at 25C. After stirring at 25C for 16 hrs, the reaction mixture was filtered and the filtrate was concentrated in vacuum to give product which was purified by prep. HPLC, and the eluents were washed with sat.NaHCO, , dried over Na2S04, filtered and concentrated to give I-A6 (25 mg, ) and I- A7 (40 mg, ) as a solid, which were further purified by prep-TLC (DCM: Acetone = 2:3) to give pure I-A6 (4 mg, 1.8%) and I-A7 (20 mg, 9%) as a solid. (0792) [0507] I-A6: 1H NMR (400 MHz, CDCl3) d 9.26 (s, 1H), 8.19-8.14 (m, 1H), 7.98 (s, (0793) 1H), 7.55-7.50 (m, 1H), 5.35-5.18 (m, 2H), 2.70-2.61 (m, 1H), 2.29-2.09 (m, 3H), 1.84-1.71 (m, 2H), 1.55-1.40 (m, 10H), 1.38-1.35 (m, 4H), 1.31-1.22 (m, 3H), 1.20-1.11 (m, 2H), 1.08- (0794) 1.00 (m, 1H), 0.94 (s, 3H), 0.81 (s, 3H), 0.70 (s, 3H); LC-ELSD purity 99%; MS ESI calcd. for C29H42N302 [M+H]+ 464, found 464. (0795) [0508] I-A7: 1H NMR (400 MHz, CDCl3) d 8.79 (s, 1H), 8.36-8.31 (m, 1H), 8.09 (s, (0796) 1H), 7.67-7.62 (m, 1H), 5.31-5.19 (m, 2H), 2.70-2.62 (m, 1H), 2.29-2.11 (m, 3H), 1.81-1.69 (m, 2H), 1.64-1.60 (m, 1H), 1.53-1.39 (m, 9H), 1.36 (s, 3H), 1.35-1.21 (m, 4H), 1.20-1.13 (0797) (m, 2H), 1.08-1.01 (m, 1H), 0.94 (s, 3H), 0.82 (s, 3H), 0.72 (s, 3H); LC-ELSD purity 99%; MS ESI calcd. for C29H42N302 [M+H]+ 464, found 464.

Molecular Weight:119.12
XLogP3:0.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:119.048347172
Monoisotopic Mass:119.048347172
Topological Polar Surface Area:41.6
Heavy Atom Count:9
Complexity:105
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes