5-Bromo-2-methyl-3-nitropyridine

5-Bromo-2-methyl-3-nitro-pyridine diethyl (5-bromo-3-nitropyridin-2-yl)propanedioate (6.8 g, 18.8 mmol) was refluxed in 290 ml of 6M HCl overnight. The reaction mixture was allowed to cool down to room temperature, and the mixture was neutralized with NaOH in an ice bath to pH 10. The solution was extracted with dichloromethane (DCM), dried, and evaporated to a yellow solid, 3.88 g, in 95percent yield.Step 2 - Synthesis of 5-bromo-2-methyl-3-nitropyridineA mixture of diethyl 2-(5-bromo-3-nitropyridin-2-yl)malonate (1.2 g, 3.3 mmol) was added to 7.0 N HCl (10 mL) and heated to refluxed for 5 hours, the reaction was cooled to room temperature and extracted with DCM : MeOH = 10 : 1, the organic phase was dried (NaStep 2 - Synthesis of 5-bromo-2-methyl-3-nitropyridine A mixture of diethyl 2-(5-bromo-3-nitropyridin-2-yl)malonate (1.2 g, 3.3 mmol) was added to 7.0 N HCl (10 mL) and heated to refluxed for 5 hours, the reaction was cooled to room temperature and extracted with DCM : MeOH = 10 : 1, the organic phase was dried (NaExample 635-bromo-2-methyl-3-nitropyridineA stirred mixture of diethyl 2-(5-bromo-3-nitropyridin-2-yl)malonate (12.5 g, 34.6 mmol) in HCI (7 N in water, 200 ml.) is heated at reflux for 18 hours. The mixture is cooled to room temperature and extracted with CHThe title compound is prepared as described in WO 2006/103449 (intermediate 24).C-l (40.0 g, 111 mmol) is taken up in 110 mL IN HC1 and the reaction mixture is stirred under reflux for 3 h. After cooling to RT, the aqueous phase is extracted with DCM, the combined organic layers are washed with saturated aqueous NaHC03-solution, dried over MgS0The title compound is prepared as described in WO 2006/103449 (intermediate 24).C-l (40.0 g, 111 mmol) is taken up in 110 mL IN HC1 and the reaction mixture is stirred under reflux for 3 h. After cooling to RT, the reaction mixture is extracted with DCM, the combined organic layers are washed with saturated aqueous NaHC0The title compound is prepared as described in (intermediate 24). C-1 (40.0 g, 111 mmol) is taken up in 110 mL 1N HCl and the reaction mixture is stirred under reflux for 3 h. After cooling to RT, the reaction mixture is extracted with DCM, the combined organic layers are washed with saturated aqueous NaHCOThe title compound is prepared as described in WO 2006/103449 (intermediate 24). C-1 (40.0 g, 111 mmol) is taken up in 110 mL 1N HCl and the reaction mixture is stirred under reflux for 3 h. Step 2: 5-Bromo-2-methyl-3-nitropyridine; To diethyl (5-bromo-3-nitropyridin-2-yl)malonate (66 g, 0.18 mol) was added water (250 mL) and 12 M HCl (360 mL, 4.32 mol). The mixture was heated at 105 A mixture of the diethyl 2-(5-bromo-3-nitropyridin-2-yl)malonate (31.8 g, 88 mmol) in aqueous hydrochloric acid (6M, 1.4 L) was stirred at reflux for 18 hours.A mixture of the diethyl 2-(5-bromo-3-nitropyridin-2-yl)malonate (31 .8 g, 88 mmol) in aqueous hydrochloric acid (6M, 1 .4 L) was stirred at reflux for 18 hours. The reaction mixture was cooled to ambient temperature and added very slowly to a saturated aqueous solution of aqueous sodium bicarbonate (4 L) at 0 °C. The mixture was then extracted with dichloromethane (7 L), dried over magnesium sulfate and the solvent removed in vacuo to give 5-bromo-2-methyl-3-nitropyridine as an orange oil (13.8 g, 63.9 mmol, 72 percent) which solidified upon standing. A mixture of the diethyl 2-(5-bromo-3-nitropyridin-2-yl)malonate (31.8 g, 88 mmol) in aqueous hydrochloric acid (6 M, 1.4 L) was stirred at reflux for 18 hours. The reaction mixture was cooled to ambient temperature and added very slowly to a saturated aqueous solution of aqueous sodium bicarbonate (4 L) at 0° C. The mixture was then extracted with dichloromethane (7 L), dried over magnesium sulfate and the solvent removed in vacuo to give 5-bromo-2-methyl-3-nitropyridine as an orange oil (13.8 g, 72percent) which solidified upon standing. Intermediate 7; Preparation of N-(5-bromo-2-methyl-3-pyridinyl)cyclopropanesulfonamide; a) 5-bromo-2-methyl-3-nitropyridine; Sodium hydride (1.31 g, 54.8 mmol, 2.19 g of 60percent in mineral oil) was suspended in dry THF (70 mL) and to this suspension was added 5-bromo-2-chloro-3-nitropyridine as a solid. An ambient water bath was placed under the reaction and a solution of diethyl malonate in dry THF (15 mL) was added carefully via addition funnel. Observed a vigorous evolution of gas. After 2 hours additional sodium hydride (0.202 g, 8.42 mmol, 0.337 g of 60percent in mineral oil) was added and the reaction was stirred for 1.5 hours. The reaction was concentrated in vacuo, diluted with 6N HCl (100 ml), and refluxed overnight. The reaction was concentrated in vacuo and diluted with saturated sodium carbonate to pH 9. The basic aqueous mixture was diluted with dichloromethane and filtered through filter paper to remove an insoluble green solid. The filtrate was transferred to a separatory funnel and the layers were separated. The dichloromethane was washed with saturated sodium chloride (aq), dried over sodium sulfate, filtered and concentrated to give the title compound (5.79 g, 63.3percent) as an orange oil. MS (ES)Example 66; N- [2-Methyl-5 -(6-quinolinyl)-3 -pyridinyljmethanesulfonamide; a) 5-bromo-2-methyl-3-nitropyridine; Sodium hydride (1.31 g, 54.8 mmol; 2.19 g of 60percent in mineral oil) was suspended in dry THF (70 mL) and to this suspension was added 5-bromo-2-chloro- 3-nitropyridine as a solid. An ambient water bath was placed under the reaction and a solution of diethyl malonate in dry THF (15 mL) was added carefully via addition funnel. A vigorous evolution of gas was observed. After 2 hours additional sodium hydride (0.202 g, 8.42 mmol, 0.337 g of 60percent in mineral oil) was added and the reaction was stirred for 1.5 hours. The reaction was concentrated in vacuo, diluted with 6 N HCl (100 mL), and heated at reflux overnight. The reaction was concentrated in vacuo and diluted with saturated sodium carbonate until the pH = 9. The basic aqueous mixture was diluted with dichloromethane and filtered through filter paper to remove an insoluble green solid. The filtrate was transferred to a separatory funnel and the layers were separated. The dichloromethane was washed 5 -Bromo-2-methyl-3 -nitropyridineSodium hydride (1.31 g, 54.8 mmol, 2.19 g of 60percent in mineral oil) was suspended in dry THF (70 mL) and to this suspension was added 5 -bromo-2-chloro-3 -nitropyridine as a solid. An ambient water bath was placed under the reaction and a solution of diethyl malonate in dry THF (15 mL) was added carefully via addition funnel. Observed a vigorous evolution of gas. After 2 hours additional sodium hydride (0.202 g, 8.42 mmol, 0.337 g of 60percent in mineral oil) was added and the reaction was stirred for 1.5 hours. The reaction was concentrated in vacuo, diluted with 6N HCl (100 ml), and refluxed overnight.

Molecular Weight:217.02
XLogP3:1.8
Hydrogen Bond Acceptor Count:3
Exact Mass:215.95344
Monoisotopic Mass:215.95344
Topological Polar Surface Area:58.7
Heavy Atom Count:11
Complexity:159
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes