2-Pyridinecarbonitrile,5-formyl-(9CI)

1.04 g (8.2 mmol) [OXALYLCHLORIDE] are dissolved in 8 ml dichloromethane. [AT-78°C, ] 1.28 g (16.4 mmol) dimethylsulfoxide are added dropwise. The solution is stirred at [- 78°C] for 20 minutes, then 1 g (7.46 mmol) of the compound of Example 5A, dissolved in 7 ml dichloromethane, is added, and stirring at-78°C is continued for another 2 hours. 3.4 g (33.6 mmol) triethylamine are then added dropwise, and after warming up to room temperature, the mixture is purified by column chromatography (silica, eluent cyclohexane to cyclohexane/ethyl acetate 2: 1). Yield: 0.76 g (77percent ofth.) Analytical data: see aboveExample 3A; 5-Formyl-2-pyridinecarbonitrile 1.04 g (8. 2 mmol) oxalylchloride are dissolved in 8 ml dichloromethane. At-78°C, 1.28 g (16.4 mmol) dimethylsulfoxide are added dropwise. The solution is stirred at-78°C for 20 minutes, then 1 g (7.46 mmol) of the compound of Example 2A, dissolved in 7 ml dichloromethane, is added, and stirring at-78°C is continued for another 2 hours. 3.4 g (33.6 mmol) triethylamine are then added dropwise, and after warming up to room temperature, the mixture is purified by column chromatography (silica, eluent: cyclohexane to cyclohexane/ethyl acetate 2: 1). Yield: 0.76 g (77percent of th.) Mp.: 80-82°C HPLC (method 4): Rt = 2.13 min MS (ESIpos): m/z = 133 (M+H) + 'H-NMR (400 MHz, DMSO-d6) : 8 = 10. 18 (s, 1H), 9.21 (m, 1H), 8.49 (m, 1H), 8.27 (m, 1H) ppm.In THF (5.0 mL) was dissolved 5-(1, 3-dioxolan-2-yl)picolinonitrile (478 mg, 2.71 mmol) obtained in Step 2, and 1 mol/L hydrochloric acid (5.0 mL) was added under a nitrogen atmosphere at room temperature. The mixture was stirred at the same temperature for 16 hours and further stirred at 50° C. for 13 hours. The reaction mixture was neutralized with a saturated aqueous sodium bicarbonate solution. Extraction with ethyl acetate, washing with saturated brine and drying over anhydrous sodium sulfate were performed. After filtration, the solvent in the filtrate was evaporated under reduced pressure to give 5-formylpicolinonitrile (364 mg, 100percent yield).Prepared in analogy to the procedure of Dodd, D. et al. [[JORG. CHEM.] 1992, [57, ] 7226-7234]: To a stirred solution of [5- (1, 3-DIOXOLAN-2-YL)-2-PYRIDINECARBONITRILE] (Example 2A; 850 mg, 4.8 mmol) in acetone/water 85: 15 (59.5 ml) is given p- toluenesulphonic acid (102 mg, 0.59 mmol). The reaction is stirred at reflux overnight (18 h), then additional p-toluenesulphonic acid (50 mg) and water (5 ml) are added. The reaction is stirred at reflux for an additional 48 h. The solution is cooled to room temperature and quenched with saturated sodium bicarbonate solution. The product is extracted with ethyl acetate (3 x 100 ml), dried over magnesium sulphate monohydrate, filtered and concentrated in vacuo. The crude product is purified by preparative HPLC to afford a pale yellow solid. Yield: [0.] 66 g (93percent [OF TH.)] Mp.: [80-82°C] HPLC (method 4): 2.13 min. MS (ESIpos): [M/Z] [133 (M+H) +] [1H-NMR] (400 MHz, [DMSO-D6)] : 8 = [10. 18 (S, 1H), ] 9.21 (m, 1H), 8.49 (m, [1H), ] 8.27 (m, [1H)] ppm.1.04 g (8.2 mmol) oxalylchloride are dissolved in 8 ml dichloromethane. At-78 C, 1.28 g (16.4 mmol) dimethylsulfoxide are added dropwise. The solution is stirred at - 78 C for 20 minutes, then 1 g (7.46 mmol) of Example 51A, dissolved in 7ml dichloromethane, is added, and stirring at-78 C is continued for another 2 hours. 3.4 g (33.6 mmol) triethylamine are then added dropwise, and after warming up to room temperature, the mixture is purified by column chromatography (silica, eluent cyclohexane to cyclohexane/ethyl acetate 2: 1). Yield: 0.76 g (77percentof th.) Mp.:80-82 C HPLC (method 4): Rt = 2.13 min. MS (ESIpos) : m/z = 133 [M+H]+'H-NMR (400 MHz, DMSO-d6):8 = 10.18 (s, 1H) ; 9.21 (m, 1H); 8.49 (m, 1H) ; 8.27 (m, 1H) ppm.A suspension of 2-bromo-5-formylpyridine (940 mg, 5.05 mmol) and copper (I) cyanide (679 mg, 7.58 mmol) in DMF (8.4 mL) was stirred at 120° C. for 1.5 hours, cooled to RT, and partitioned between water and EtOAc. The solids were removed from the aqueous layer by filtration, and the filtrate was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated. The crude product was purified by silica-gel chromatography, eluting with a gradient of 40percent-60percent (40percent ethyl acetate in heptane) in heptane, to provide the title compound (236 mg, 1.786 mmol) as white solid. LC/MS (ESIA suspension of 2-bromo-5-formylpyridine (940 mg, 5.05 mmol) and copper (I) cyanide (233 xL, 7.58 mmol) in DMF (8.4 mL) was stirred at 120°C for 1.5 hours, cooled to RT, and partitioned between water and EtOAc. The solids were removed from the aqueous layer by filtration, and the filtrate was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated. The crude product was purified by silica-gel chromatography, eluting with a gradient of 40percent-60percent (40percent ethyl acetate in heptane) in heptane, to provide the title compound (236mg, 1.786 mmol) as white solid. LC/MS (ESIA suspension of 2-bromo-5-formylpyridine (940 mg, 5.05 mmol) and copper (I) cyanide (233 μL, 7.58 mmol) in DMF (8.4 mL) was stirred at 120° C. for 1.5 hours, cooled to RT, and partitioned between water and EtOAc. The solids were removed from the aqueous layer by filtration, and the filtrate was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated. The crude product was purified by silica-gel chromatography, eluting with a gradient of 40percent-60percent (40percent ethyl acetate in heptane) in heptane, to provide the title compound (236 mg, 1.786 mmol) as white solid. LC/MS (ESIStep 1: (0581) A mixture of 6-bromonicotinaldehyde (11.2 g, 60 mmol) and CuCN (8.06 g, 90 mmol) in DMF (100 mL) was heated at 120° C. for 3 h under NA suspension of 2-bromo-5-formylpyridine (940 mg, 5.05 mmol) and copper (I) cyanide (233 µL, 7.58 mmol) in DMF (8.4 mL) was stirred at 120°C for 1.5 hours, cooled to RT, and partitioned between water and EtOAc. The solids were removed from the aqueous layer by filtration, and the filtrate was extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated. The crude product was purified by silica-gel chromatography, eluting with a gradient of 40percent-60percent (40percent EtOAc in heptane) in heptane, to provide the title compound (236mg, 1.786 mmol) as white solid. LC/MS (ESICompound 21C (1 g, 7.57 mmol), 2-Amino-4, 6-dichlorophenol and acetic acid (10 drops) were dissolved in 30 mL of methanol.Sodium cyanoborohydride (2.38 g, 37.8 mmol) was added at room temperature with stirring.The reaction solution was stirred at 60 C overnight, and after cooling to room temperature, 100 mL of water was added.The precipitate is precipitated and filtered to obtain the target crude product.The crude product was isolated by reverse phase column chromatography to afford pale yellow compound 21 (1.2 g, 53% yield)A solution of 2-((lr, 4r)-4-((5- nitro- 1 -(phenyl sulfonyl)- 1H-pyrrolo[2, 3 -b]pyridin-4-yl)amino)cyclohexyl)acetonitrile(Intermediate 1, 152 mg, 0.346 mmol),

Molecular Weight:132.12
XLogP3:0.4
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:132.032362755
Monoisotopic Mass:132.032362755
Topological Polar Surface Area:53.8
Heavy Atom Count:10
Complexity:170
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes