2-Methyl-4-nitropyridine

Yellow Solid

a) b 4-Bromo-2-picoline A mixture of b) 4-Bromo-2-picoline A mixture of The mixture of diethyl malonate (80 ml, 0.5 mol) and sodium (2.76 g, 0.12 mol) was heated to 90 C in an oil bath and stirred for 1 h.After heating to 120 C for 45 min, it was cooled to room temperature.2-Chloro-4-nitropyridine (15.6 g, 0.1 mol) in toluene solution was added dropwise, and the reaction mixture was heated to 110 C for 1.5 h, cooled to room temperature and stirred for 15 h.The solvent was evaporated under reduced pressure, and then 6N hydrochloric acid (100 ml) was evaporated.The pH was made alkaline with a saturated sodium carbonate solution, extracted with ethyl acetate, combined with a base phase and dried over anhydrous sodium sulfate.Concentration by suction filtration gave Example 93 2-chloro-5, 11-dihydro-11-ethyl-8-(2-methylpyrid-4-yloxy)methyl-5-methyl-6H-dipyrido[3, 2-b;2', 3'-e][1, 4]diazepin-6-one Using a procedure analogous to that described in Example 91, except potassium hydride was employed as the base instead of sodium hydride, the title compound, m.p. 163-164 C., was prepared from 2-chloro-5, 11-dihydro-11-ethyl-8-hydroxymethyl-5-methyl-6H-dipyrido-[3, 2-b:2', 3'-e][1, 4]diazepin-6-one and General procedure: Under an argon atmosphere, a Schlenk tube was charged with MCM-41-2N-Cu(OAc)2(46 mg, 0.025 mmol), nitroarene 1 (0.5 mmol), phenol 2 (1.0 mmol), Cs2CO3 (1.0 mmol) and DMF (3 mL). The reaction mixture was stirred at 100 C for 5 h under Ar. After being cooled to room temperature, the mixture was diluted with ethyl acetate (20 mL) and filtered. The MCM-41-2N-Cu(OAc)2 catalyst was washed with distilled water (2 × 5 mL), DMF (2 × 5 mL) and EtOH (2 × 5 mL) and could be reused in the next run. The filtrate was washed with water (2 × 10 mL) and dried over anhydrous MgSO4. After removal of the solvent under reduced pressure, the residue was purified by column chromatography (EtOAc/hexane) on silica gel to afford the desired product 3.General procedure: Under an argon atmosphere, a Schlenk tube was charged with MCM-41-2N-Cu(OAc)2(46 mg, 0.025 mmol), nitroarene 1 (0.5 mmol), phenol 2 (1.0 mmol), Cs2CO3 (1.0 mmol) and DMF (3 mL). The reaction mixture was stirred at 100 C for 5 h under Ar. After being cooled to room temperature, the mixture was diluted with ethyl acetate (20 mL) and filtered. The MCM-41-2N-Cu(OAc)2 catalyst was washed with distilled water (2 × 5 mL), DMF (2 × 5 mL) and EtOH (2 × 5 mL) and could be reused in the next run. The filtrate was washed with water (2 × 10 mL) and dried over anhydrous MgSO4. After removal of the solvent under reduced pressure, the residue was purified by column chromatography (EtOAc/hexane) on silica gel to afford the desired product 3.

Pharmaceutical intermediates.

Molecular Weight:138.12
XLogP3:0.9
Hydrogen Bond Acceptor Count:3
Exact Mass:138.042927438
Monoisotopic Mass:138.042927438
Topological Polar Surface Area:58.7
Heavy Atom Count:10
Complexity:132
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes