* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
To a suspension of sodium hydride (8.76 g, 60% dispersion in m ineral oil) in THF (340mL) under nitrogen atmosphere was added <strong>[21427-62-3]2,5-dichloro-3-nitropyridine</strong> (40g, 207mmol followed by diethylmalonate (63.2mL, 412mmol dissolved in 63mL of THF) drop wise at room temperature for 20min. A vigorous evolution of gas was observed. After 2 h, additional sodium hydride (1. 1 9 g, 60% dispersion in mineral oil) was added and the reaction mixture was then stirred at room temperature for 1 .5h. The reaction mixture was concentrated under reduced pressure and diluted with 6N I-1C1 (400mL) and refluxed for 12.5 h. The resulting mixture was concentrated under reduced pressure and diluted with saturated sodium carbonate solution (400mL) until pH=9, then diluted with dichloromethane (400 mL), stirred for 1 0 min, and filtered to remove an insoluble green solid; from the filtrate, the organic layer was separated and washed with brine, dried over anhydrous Na2S04 and concentrated to afford 5-chloro-2-methyl-3-nitropyridine (26 g crude) as a brown liquid which was directly used in the next step without further purification.
(S)-3-[(S)-2-(5-[(5-chloro-2-methylpyridin-3-yl)amino]methyl}thiophene-2-carboxamido)-3-cyclopentylpropanamido]cyclobutyl 2,6-bis[(tert-butoxycarbonyl)amino]hexanoate[ No CAS ]
(S)-3-[(S)-2-(5-[(5-chloro-2-methylpyridin-3-yl)amino]methyl}thiophene-2-carboxamido)-3-cyclopentylpropanamido]cyclobutyl 2,6-diaminohexanoate trihydrochloride[ No CAS ]
With tin(II) chloride dihdyrate; In ethyl acetate; at 85.0℃; for 3h;Inert atmosphere;
To a solution of <strong>[1211533-93-5]5-chloro-2-methyl-3-nitropyridine</strong> (26g, 15 1 mmol) in ethyl acetate (850mL) under nitrogen atmosphere was added SnC12.2H20 (136g, 603 mmol) at room temperature. The reaction mixture was heated to 85C for 3h. Concentration of the reaction mixture under reduced pressure afforded a pale yellow slurry which was basified with I N NaOH solution (520mL). The resulting mixture was diluted withdichloromethane (750mL) and stirred for 10 minutes. The mixture was then fi ltered through a celite pad to remove undissolved solids. The filtrate's organic layer was separated, dried over anhydrous Na2S04 and concentrated under reduced pressure. The crude compound was purified by column chromatography on silica gel ( 100-200 mesh) using 0-35% ethyl acetate in petroleum ether to afford desired 5-chloro-2-methylpyridine- 3-amine (18 g) as a brown solid.
Diethyl malonate reacted with sodium to form a salt,Then 2 methyl-3-nitro-5-chloropyridine toluene solution was added dropwise condensation reaction,Followed by decarboxylation under acidic conditions to give 2,5-dimethyl-3-nitropyridine,The diethyl malonate, alkali metal,2 methyl-3-nitro-5-chloropyridine molar ratio of 4.2: 1.4: 1.2;
With sodium; In toluene;
Diethyl malonate and sodium react to form a salt, and then a <strong>[1211533-93-5]2-methyl-3-nitro-5-chloropyridine</strong> in toluene solution is added dropwise to carry out a condensation reaction, followed by decarboxylation under acidic conditions to obtain 2,5-dimethyl-3-nitropyridine, the molar ratio of diethyl malonate, alkali metal, 2 methyl-3-nitro-5-chloropyridine is 4.2:1.4:1.2;
With sodium; In toluene;Acidic conditions;
Diethyl malonate reacts with sodium to form a salt, and then a toluene solution of <strong>[1211533-93-5]2-methyl-3-nitro-5-chloropyridine</strong> is added dropwise for condensation reaction, and then decarboxylated under acidic conditions to obtain 2,5-dimethyl-3-nitropyridine, the molar ratio of the diethyl malonate, alkali metal, and <strong>[1211533-93-5]2-methyl-3-nitro-5-chloropyridine</strong> is 4.2: 1.4: 1.2;
N-(5-chloro-2-methyl-6-(1-methyl-1H-pyrazol-3-yl)pyridin-3-yl)-1-(1-oxo-1,2-dihydroisoquinolin-5-yl)-5- (trifluoromethyl)-1H-pyrazole-4-carboxamide[ No CAS ]
5-chloro-2-methyl-3-nitropyridine 1-oxide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
2.4 g
With 3-chloro-benzenecarboperoxoic acid; In dichloromethane; at 20.0℃; for 72h;
A mixture of <strong>[1211533-93-5]5-chloro-2-methyl-3-nitropyridine</strong> (3.0 g, 17.4 mmol) and mCPBA (85%, 7.06 g, 34.8 mmol) in CH2Cl2 (60 mL) was stirred at rt for 72 h. The reaction mixture was quenched with 60 mL sat. Na2SO3 aq. Sat. K2CO3 aq was added to adjust the mixture pH to 9?10 and the mixture was extracted with CH2Cl2 (100 mL*3). The organic layer was separated, dried over Na2SO4, filtered and the filtrate concentrated to afford a yellow solid. The solid was purified by flash column chromatography over silica gel (eluent: petroleum ether/EtOAc 100/0 to petroleum ether/EtOAc 0/100). The desired fractions were collected and the solvent was concentrated to dryness under reduced pressure to afford the desired product as a yellow solid (2.4 g, yield: 73.2%). 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 2.65 (s, 3H), 7.71 (d, J=1.54 Hz, 1H), 8.46 (d, J=1.54 Hz, 1H).
tert-butyl (6-(4-((5-chloro-2-methyl-6-(2H-1,2,3-triazol-2-yl)pyridin-3-yl)carbamoyl)-5-(trifluoromethyl)-1H-pyrazol-1-yl)-3-fluoropyridin-2-yl)carbamate[ No CAS ]
N-(5-chloro-2-methyl-6-(2H-1,2,3-triazol-2-yl)pyridin-3-yl)-1-(8-fluoroimidazo[1,2-a]pyridin-5-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide[ No CAS ]
N-(5-chloro-2-methyl-6-(2H-1,2,3-triazol-2-yl)pyridin-3-yl)-1-(1-oxo-1,2-dihydroisoquinolin- 5-yl)-5-(trifluoromethyl)-1H- pyrazole-4-carboxamide[ No CAS ]
1-(benzo[d][1,2,3]thiadiazol-7- yl)-N-(5-chloro-2-methyl-6-(2H- 1,2,3-triazol-2-yl)pyridin-3-yl)- 5-(trifluoromethyl)-1H-pyrazole- 4-carboxamide[ No CAS ]
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
