6-chloro-4-Methoxypyridin-3-aMine

A mixture of 2-chloro-4-methoxy-5-nitropyridine (208 mg, 1.10 mmol), ammonium chloride (295 mg, 5.52 mmol) and iron powder (246mg, 4.4immol) in ethanol (5mL) and water (0.5mL) was heated at 80 oC for 18 h. The mixture was cooled and filtered through a Celite cartridge and washed through with methanol. The combined filtrate and washing was evaporated, and the residue partitioned between DCM (10 mL)and water (10 mL), the organic phase was washed further with water (10 mL), and the aqueous washes were combined and extracted with DCM (3 x 5 mL). The organic extracts were combined and filtered through a hydrophobic fit, and the solvent was removed by evaporation to give the product as an off-white solid (155 mg, 89percent). ‘H NMR (400 MHz, CDC13): ö 7.73 (s, 1H); 6.71 (s, 1H); 3.90 (s, 3 H); 3.71 (s, 2H).To a suspension of 2-chloro-4-methoxy-5-nitropyridine (300 mg, 1.59 mmol), prepared according to a literature procedure (PCT Int. Appl. (2003), WO 2003080610 Al 20031002) in EtOH (3 mL) was added SnClTo a solution of XII-1 (0.50 g, 1 .97 mmol) in pyridine (10 mL) was added X-1 (0.18 g, 1 .25 mmol) and DMAP (0.012 g, 0.09 mmol). The reaction mixture was heated at 80 C for 16h. Progress of the reaction was monitored by TLC and LCMS. After completion, the reaction mixture was concentrated under vacuum. The residue was diluted with H20 (100 mL), 1 N HCI (50 mL) and extracted with EtOAc (100 mL). The organic layer was separated, dried over anhydrous Na2S04 and concentrated under vacuum. The crude obtained was purified by column chromatography (silica, 100-200 mesh, 40% EtOAc in hexane) to afford 6-chloro-N-(2, 5-difluoropyridin-3-yl)-1H-indole-3-sulfonamide 1-1 (0.05 g) as an off-white solid. (1207) Yield: 7%. (1208) Basic LCMS Method 1 (ES ): 342 (M-H)-, 97% purity. (1209) 1H NMR (400 MHz, DMSO-cfe) d 7.25 (dd, J=8.31 , 1.47 Hz, 1 H), 7.54 (s, 1 H), 7.71-7.81 (m, 2H), 7.89 (s, 1 H), 8.16 (d, J=2.93 Hz, 1 H), 10.73 (brs, 1 H), 12.22 (brs, 1 H).Trimethylaluminum (7.6 mL, 2.0 M in toluene, 15 mmol) was added slowly to a 0 C. mixture of To a mixture of To a solution of A mixture of 5-chlorothiophene-2-boronic acid (1.5 eq, 154 mg), 6-chloro-4-methoxy- pyridin-3-ylamine (1 eq, 100 mg), K3PO4 (3 eq, 602 mg) and tetrakis(triphenylphosphine)palladium(0) (0.1 eq, 58 mg) in 1.4-dioxane (3 mL) was heated at 140C for 30 min in microwave. Reaction mixture was diluted with water (5 mL), extracted with EtOAc (3 x 10 mL), dried and concentrated. The residue was purified by silica chromatography (EtOAc/cyclohexane; 0:100 to 20:80) to give the desired compound.

Molecular Weight:158.58
XLogP3:1.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:158.0246905
Monoisotopic Mass:158.0246905
Topological Polar Surface Area:48.1
Heavy Atom Count:10
Complexity:112
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes