* 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.
Step 4 4-chloro-3-nitro-2-picoline A mixture of 4-hydroxy-3-nitro-2-picoline (820 mg, 5.32 mmol) and phosphorous pentachloride (1.11 g, 5.32 mmol) in phosphorous oxychloride (6 mL) was heated for 2 hours in a 100° C. oil bath. The phosphorous oxychloride was removed under vacuum and after cooling to room temperature, the residue was partitioned between ice (10 mL) and methylene chloride (10 mL). The aqueous layer was re-extracted with additional methylene chloride (2*10 mL) and the combined extracts were dried with magnesium sulfate, filtered and gave the title compound as a light brown solid upon evaporation (0.787 g). 1 H NMR (CDCl3, 300 MHz) delta2.60 (s, Me),7.35 (d, ArH) and 8.51 (d, ArH).
6-methyl-2-thioxo-2,3-dihydrothiazolo[4,5-c]pyridine[ No CAS ]
4-chloro-3-nitro-2-(acetoxymethyl)pyridine[ No CAS ]
[ 23056-35-1 ]
6-hydroxymethyl-2-thioxo-2,3-dihydrothiazolo[4,5-c]pyridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With carbon disulfide; sodium sulfide nonahydrate; hydrogen sulfide; In water;
Step 7 6-hydroxymethyl-2-thioxo-2,3-dihydrothiazolo[4,5-c]pyridine A suspension of sulfur (0.5 g, 15.6 mmol) and sodium sulfide nonahydrate (1.84 g, 7.66 mmol) in water (5 mL) was heated in a 50° C. oil bath for 15 minutes. The amber colored solution was cooled to room temperature and the 2:1 mixture of 4-chloro-3-nitro-2-acetoxymethylpyridine/<strong>[23056-35-1]4-chloro-3-nitro-2-picoline</strong> (0.25 g, 0.36 mmol) and carbon disulfide (2 mL, 33.4 mmol) were added, and the mixture was heated in a 70° C oil bath for 18 hours under a nitrogen atmosphere. Workup and chromatography as described in Step 3 of Preparative Example 4 afforded an approximately 4:1 ratio mixture of the title compound and 6-methyl-2-thioxo-2,3-dihydrothiazolo[4,5-c]pyridine (88 mg), as observed by 1 H NMR. 1 H NMR (DMSO-d6, 300 MHz) delta4.83 (s, CH2 OH), 7.75 (d, ArH) and 8.21 (d, ArH).
4-chloro-3-nitro-2-(acetoxymethyl)pyridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In dichloromethane; acetic anhydride; ethyl acetate;
Step 6 4-chloro-3-nitro-2-(acetoxymethyl)pyridine A 45:55 mixture of <strong>[23056-35-1]4-chloro-3-nitro-2-picoline</strong> N-oxide and <strong>[23056-35-1]4-chloro-3-nitro-2-picoline</strong> (0.48 g, 1.15 mmol) in acetic anhydride (5 mL, 53 mmol) was placed in a 60° C. oil bath for 1 hour. The temperature of the oil bath was then increased to 70° C. over the next 1.5 hours. The solution was cooled to room temperature, evaporated and partitioned between methylene chloride (20 mL) and saturated aqueous potassium carbonate (120 mL). The aqueous layer was re-extracted with more methylene chloride (2*20 mL) and the combined extracts were dried with magnesium sulfate, filtered and evaporated to a foam (0.43 g), The foam was dissolved in methylene chloride and was placed on preparative silica plates (5*1000 micron, analtech, 20*20 cm) which were developed with 5percent ethyl acetate in methylene chloride and eluted with ethyl acetate to give an approximately 1:2 mixture of the title compound and 4-chloro-3-nitro-2 -picoline(0.25 g). 1 H NMR (CDCl3, 400 MHz) delta2.15 (s, OAc), 5.16 (s, CH2 OAc),7.38 (d, ArH) and 8.47 (d, ArH).
Step 5 <strong>[23056-35-1]4-chloro-3-nitro-2-picoline</strong> N-oxide <strong>[23056-35-1]4-chloro-3-nitro-2-picoline</strong> (0.787 g, 4.6 mmol) was dissolved in a mixture of trifluoroacetic acid (3 mL) and 32percent peracetic acid (2 mL) and was heated in a 60° C. oil bath for 4 hours, with an addition of 32percent peracetic acid at 2 hours (2 mL). The solution was cooled to room temperature and was partitioned between methylene chloride (30 mL) and saturated aqueous potassium carbonate (30 mL). The aqueous layer was re-extracted with more methylene chloride (2*20 mL) and the combined extracts were dried with magnesium sulfate, filtered and evaporated to give a 45:55 mixture of the title compound and <strong>[23056-35-1]4-chloro-3-nitro-2-picoline</strong>(0.5 g). 1 H NMR (CDCl3, 300 MHz) delta2.60 (s, Me), 7.35 (d, ArH) and 8.51 (d, ArH).
When in accordance with the procedure of example 1, equal molar amounts of the following are substituted for 3-nitro-2-chloropyridine:...2-chloro-3-nitro-5-methylpyridine,2-chloro-3-nitro-6-methylpyridine,2-chloro-3-nitro-5,6-dimethylpyridine,2-chloro-3-nitro-6-methoxypyridine, and4-chloro-3-nitro-2-methylpyridine,
22
[ 23056-35-1 ]
(S)-(2-chloro-3-(trifluoromethyl)phenyl)(1-(5-fluoropyrimidin-2-yl)-4-methyl-1,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridin-5-yl)methanone[ No CAS ]
(R)-(2-chloro-3-(trifluoromethyl)phenyl)(1-(5-fluoropyrimidin-2-yl)-4-methyl-1,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridin-5-yl)methanone[ No CAS ]
5-fluoro-N-(2-methyl-3-nitropyridin-4-yl)pyrimidin-2-amine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
38%
With (2-fluoro-3-(trifluoromethyl)phenyl)(1-(4-fluorophenyl)-4-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone; palladium diacetate; potassium carbonate; In toluene; at 110.0℃; for 1.0h;Microwave irradiation;
(R)-(2-chloro-3-(trifluoromethyl)phenyl)(1-(5-fluoropyrimidin-2-yl)-4-methyl-1,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridin-5-yl)methanone[ No CAS ]
(S)-(2-chloro-3-(trifluoromethyl)phenyl)(1-(5-fluoropyrimidin-2-yl)-4-methyl-1,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridin-5-yl)methanone[ No CAS ]
N-[1-(4-methoxyphenyl)piperidin-4-yl]-2-methyl-3-nitropyridin-4-amine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With sodium chloride; sodium hydrogencarbonate; N-ethyl-N,N-diisopropylamine;
1) Production Example 3 To a solution of <strong>[23056-35-1]4-chloro-2-methyl-3-nitropyridine</strong> (7 g) and 1-(4-methoxyphenyl)piperidin-4-amine (11 g) in N-methyl-2-pyrrolidone (70 mL), N,N-diisopropylethylamine (21 mL) was added, and the mixture was stirred at 140C for 2 hours. The mixture was allowed to cool to room temperature, and a saturated aqueous solution of sodium bicarbonate and water were added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate. After that, the solvent was removed by evaporation under reduced pressure. Ethyl acetate (50 mL) and hexane (200 mL) were added to the residue, and insoluble matter was collected by filtration. The resultant was dried under reduced pressure to afford N-[1-(4-methoxyphenyl)piperidin-4-yl]-2-methyl-3-nitropyridin-4-amine (11.4 g). Physicochemical data on the product is shown below. Dat: MASS (ESI, m/z) 343 [M+H]+
4-chloro-6-methyl-5-nitropyridin-2(1H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
50.0%
In a 500 mL three neck round bottom flask fitted with a Dewar condenser, ammonia (200 mL) was condensed into THF (100 mL) at -78 C. Potassium tert-butoxide (6.99 g, 62.3 mmol) was added and the resulting reaction mixture was allowed to warm to -35 C. In a separate flask containing a stirring solution of <strong>[23056-35-1]4-chloro-2-methyl-3-nitropyridine</strong> (4.3 g, 24.92 mmol) in THF (50 mL), tert-butyl hydroperoxide (5.5 M in decane) (4.76 mL, 26.2 mmol) was added at 0 C. The resulting solution was added to the reaction mixture above at -35 C (color of the reaction mixture was changed from light brown to dark brown). After stirring for 1.5 hours at -35 C the reaction mixture was quenched with saturated ammonium chloride solution (100 mL) and the reaction mixture was allowed warm to RT and stirred for 16 hours. Upon completion, the reaction mixture was concentrated under reduced pressure. The resultant brown residue was diluted with water (100 mL) and extracted with EtOAc (2 x 100 mL). The combined organic phases were washed with brine (100 mL), dried over Na2SO4 and evaporated in vacuo to give the title compound as a brown solid (2.8 g, 12.45 mmol, 50.0% yield). MS (m/z) 187.0 (M-H)-.
2'-methoxy-2-methyl-3-nitro-4,4'-bipyridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
92%
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 100℃; for 5.0h;Inert atmosphere;
A mixture of 4-chloro-2-methyl-3-nitro-pyridine (200 mg, 1.2 mmol), K2CO3 (481 mg, 3.5 mmol), Pd(dppf)Cl2 (85 mg, 0.1 mmol) and 2-methoxypyridine-4-boronicacid (213 mg, 1.4 mmol) in 1,4- dioxane (10 mL) and water (2 mL) were stirred at 100 C for 5 hours under nitrogen atmosphere. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The erode residue was purified by flash column chromatography (silica, 20% EtOAc in petroleum ether) to give 22- methoxy-2-methyl-3-nitro-4,4'-bipyridine (260 mg, yield: 92%) as a white solid. MS: m/z 245.9 (M+4).
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
