Category: pyridine-derivatives

Adding a certain compound to certain chemical reactions, such as: 951624-83-2, 5-(Trifluoromethyl)nicotinonitrile, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound, HPLC of Formula: C7H3F3N2, blongs to pyridine-derivatives compound. HPLC of Formula: C7H3F3N2

(Reference Example 117) 6-Chloro-5-(trifluoromethyl)pyridine-3-carbonitrile[0812] Urea hydrogen peroxide (0.815 g, 8.66 mmol) and trifluoroacetic anhydride (1.15 mL, 8.24 mmol) were added to a solution of 5-(trifluoromethyl)pyridine-3-carbonitrile (compound described in the pamphlet of WO2009/42694, 0.71 g, 4.12 mmol) in dichloromethane (10 mL), and the mixture was stirred overnight. A 10% sodium thiosulfate aqueous solution was added to the reaction solution, followed by extraction with dichloromethane twice. The organic layer was washed with brine and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography [elute: hexane/ethyl acetate = 88/12 – 0/100 (gradient)] to obtain a product. [0814] A solution of the obtained product in phosphoryl chloride (10 mL) was stirred at 70C for 2 hours and further for 2 hours under reflux. The reaction solution was poured to ice, followed by extraction with dichloromethane twice. Combined organic layers were washed with brine and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography [elute: hexane/ethyl acetate = 99/1 – 90/10 (gradient)] to obtain the title compound (62 mg, yield: 7%).[0815] 1H-NMR (CDCl3) delta: 8.86 (1H, d, J = 2 Hz), 8.28 (1H, d, J = 2 Hz).

At the same time, in my other blogs, there are other synthetic methods of this type of compound,951624-83-2, 5-(Trifluoromethyl)nicotinonitrile, and friends who are interested can also refer to it.

Reference:
Patent; Daiichi Sankyo Company, Limited; KOBAYASHI, Hideki; OHKAWA, Nobuyuki; TAKANO, Daisuke; KUBOTA, Hideki; ONODA, Toshio; KANEKO, Toshio; ARAI, Masami; TERASAKA, Naoki; EP2862861; (2015); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 10366-35-5, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 10366-35-5, name is 2-Chloronicotinamide, molecular formula is C6H5ClN2O, The compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

To an aqueous solution of Na2Se2 (prepared from selenium metal (1.00 g, 12.66 mmol) and NaBH4 (434 mg, 11.47 mmol) in 60 ml distilled water) was added a solution of 2-chloro-3-nicotinamide (2.00 g, 12.77 mmol) with stirring under a nitrogen atmosphere. The reaction mixture was refluxed for 2 h with stirring. After cooling to room temperature, product was extracted with a chloroform-methanol (3:1 ratio) mixture. The organic phase was separated, washed with sodium bicarbonate solution followed by water, dried over anhydrous sodium sulphate, and filtered. The filtrate was concentrated under vacuum and the residue was column chromatographed with chloroform-methanol (90:10) mixture. The solution on evaporation afforded yellow powder (yield 216 mg, 8%; due to degradation during column purification product yield was significantly reduced), m.p. 126-128 C. Anal. for C12H10N4O2Se2; Calcd: C, 36.02; H, 2.52; N, 14.00%. Found C, 34.64; H, 2.73; N, 13.47%. UV-vis (in MeOH) (lambdamax in nm): 326, 402. IR in KBr (upsilon cm-1): 3250 (NH2), 1671 (CO). 1H NMR (dmso-d6) delta: 7.28 (d, d, 6 Hz, CH-5, py); 8.35, 7.84 (NH2); 8.16 (d, 7.5 Hz, py); 8.49 (d, 5 Hz, py); 13C{1H} NMR (dmso-d6) delta: 119.7, 128.1 (C-Se),135.5, 151.5, 160.5 (C-3, py); 168.2 (CO). 77Se{1H} NMR (dmso-d6) delta: 525 ppm. Mass (m/z): 400 (M+).

According to the analysis of related databases, 10366-35-5, the application of this compound in the production field has become more and more popular.

Reference:
Article; Parashiva Prabhu; Phadnis, Prasad P.; Wadawale, Amey P.; Indira Priyadarsini; Jain, Vimal K.; Journal of Organometallic Chemistry; vol. 713; (2012); p. 42 – 50;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

The major producers of chemicals have been the Europe, Japan and China. Due to the growing call for a cleaner, greener environment, people will have to find innovative ways to maintain their relevance. Here is a compound 6959-48-4, name is 3-(Chloromethyl)pyridine hydrochloride. This compound has unique chemical properties. The synthetic route is as follows. Recommanded Product: 3-(Chloromethyl)pyridine hydrochloride

General procedure: DMF (5-10 mL/mmol). K2CO3 (10 equiv) was added and the suspensionstirred for 15 min. Then, 3-(chloromethyl) pyridiniumchloride (1.1 equiv) was added and the reaction mixture was stirredfor 48 h at room temperature. The suspension was diluted withH2O and extracted with EtOAc. The combined organic phases werewashed with H2O and brine, dried over magnesium sulfate and thesolvent was removed in vacuo. The crude products were purifiedby column chromatography [Cyclohexane/EtOAc, 3:1 4.2.2.2 tert-Butyl N-(4-methoxyphenylsulfonyl)-N-(3-pyridylmethyl)-2-amino-4-fluorobutanoate (S)-Enantiomer ((S)-14): Yield: 1512 mg (85%), greenish, viscous oil. 1H NMR (300 MHz, CDCl3): delta 1.35 (s, 9H), 1.86 (m, 1H), 2.22 (ddt, 2JH,H = 13.6 Hz, 3JH,H = 9.7 Hz, 3JH,H = 6.0 Hz, 1H), 3.86 (s, 3H), 4.19-4.45 (m, 2H), 4.36 (d, 2JH,H = 16.1 Hz, 1H), 4.49 (dd, 3JH,H = 7.7 Hz, 3JH,H = 6.6 Hz, 1H), 4.69 (d, 2JH,H = 16.2 Hz, 1H), 6.96 (dm, 3JH,H = 8.9 Hz, 2H), 7.25 (dd, 3JH,H = 7.9 Hz, 3JH,H = 4.8 Hz, 1H), 7.77 (dm, 3JH,H = 8.9 Hz, 2H), 7.82 (dm, 3JH,H = 8.4 Hz, 1H), 8.51 (s, 1H), 8.53 (s, 1H) ppm. 13C NMR (75 MHz, CDCl3): delta 27.7 (q), 31.8 (dt, 2JC,F = 20.5 Hz), 47.3 (t), 55.6 (q), 57.0 (dd, 3JC,F = 4.3 Hz), 80.1 (dt, 1JC,F = 166.3 Hz), 82.5 (s), 114.1 (d), 123.4 (d), 129.6 (d), 131.3 (s), 132.9 (s), 136.3 (d), 149.1 (d), 149.4 (d), 163.0 (s), 169.0 (s) ppm. 19F NMR (282 MHz, CDCl3): delta -221.4 (ddt, 2JH,F = 46.9 Hz, 3JH,F = 28.3 Hz, 3JH,F = 22.8 Hz) ppm. HRMS (ESI+): C21H27N2O5S+H+, calcd 439.1703, found: 439.1701; C21H27N2O5S + Na+, calcd 461.1522, found: 461.1526; (C21H27N2O5S)2+H+, calcd 877.3328, found: 877.3320; (C21H27N2O5S)2 + Na+, calcd 899.3147, found: 899.3146. MS (ESI+, daughter ion experiment): m/z (%) 439 (15) [M++H+], 383 (100) [439-C4H8], 171 (5) [C7H7O3S+], 167 (10) [383-C7H7O3S-CO2H], 92 (3) [C6H6N+]. Optical rotation (c 1.001, CHCl3): [alpha]58920 = +34.1, [alpha]57820 = +35.5, [alpha]54620 = +41.1, [alpha]43620 = +74.5, [alpha]36520 = n.d.

With the rapid development of chemical substances, we look forward to future research findings about 6959-48-4.

Reference:
Article; Behrends, Malte; Wagner, Stefan; Kopka, Klaus; Schober, Otmar; Schaefers, Michael; Kumbhar, Sadhana; Waller, Mark; Haufe, Guenter; Bioorganic and Medicinal Chemistry; vol. 23; 13; (2015); p. 3809 – 3818;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 59281-14-0, In the chemical reaction process,reaction time,type of solvent,can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product.An updated downstream synthesis route of 59281-14-0 as follows.

(B) 2-(Chloromethyl)-5-(phenylmethoxy)-4(1H)pyridinone, monohydrochloride A suspension of 2-(hydroxymethyl)-5-(phenylmethoxy)-4(1H)-pyridinone (3 g, 12.99 mmole) in chloroform (15 ml) was cooled to 0 under argon and treated with thionyl chloride (6.1 ml, 83.62 mmole). Within several minutes, a homogeneous solution was obtained. After stirring an additional 5 minutes, a cream colored solid precipitated. The cooling bath was removed and the mixture was heated at reflux for 45 minutes. The mixture was cooled to 0 and the white precipitate was filtered, washed with chloroform and hexane and dried in vacuo. The yield of the title compound was 3.65 g.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,59281-14-0, its application will become more common.

Reference:
Patent; E. R. Squibb & Sons, Inc.; US4743685; (1988); A;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 113118-81-3, name is 5-Bromonicotinaldehyde, the common compound, a new synthetic route is introduced below. Quality Control of 5-Bromonicotinaldehyde

To a solution of 5-bromonicotinaldehyde (XXXVII) (2.0 g, 10.8 mmol, 1 eq) in MeOH (20 mL) was added NaBH4 (2.4 g, 64.9 mmol, 6 eq) and the reaction mixture was stirred at room temperature for 3 h. The mixture was concentrated in vacuo and the residue was diluted in water (15 mL), the aqueous phase was extracted with DCM (10 mL x 3). The combined organic layers were dried over Mg504, filtered and concentrated in vacuo to afford (5- bromopyridin-3-yl)methanol (XLIV) (1.8 g, 9.57 mmol, 90.0% yield) as a colorless oil. ?H NMR (CDC13, 500 MHz) ppm 4.73 (s, 2H), 7.90 (s, 1H), 8.47 (s, 1H), 8.57 (s, 1H). ESIMS found for C6H6BrNO mlz 188.0 (M+H).

The synthetic route of 113118-81-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; SAMUMED, LLC.; KC, Sunil Kumar; WALLACE, David Mark; CAO, Jianguo; CHIRUTA, Chandramouli; MARAKOVITS, Joseph Timothy; BOLLU, Venkataiah; HOOD, John; (307 pag.)WO2017/23989; (2017); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 15862-30-3, With the rapid development and complex challenges of chemical substances, the synthesis of new drugs is usually one of the most effective ways to increase yield.15862-30-3, name is 3-Bromo-5-nitropyridine, molecular formula is C5H3BrN2O2, molecular weight is 202.99, as common compound, the synthetic route is as follows.

To a flask was added 3-bromo-5-nitropyridine (60 mg, 296 mumol), THF (2 mL), tert-butyl pent-4-yn-1-ylcarbamate (59.6 mg, 325 mumol), Pd(OAc)2 (3.32 mg, 14.8 mumol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (17.1 mg, 29.6 mumol) and Cs2CO3 (193 mg, 591 mumol). Then the mixture was bubbled with N2 for 5 mins and heated to reflux (70 C. oil bath) for about 4.5 hours. The mixture was filtered through celite and the filtrate was concentrated to give a brown solid. After purification via combiflash (eluted with EA/PE=020%40%), tert-butyl N-[5-(5-nitro-3-pyridyl)pent-4-ynyl]carbamate (Compound 72A) was obtained as pale brown oil.

Statistics shows that 15862-30-3 is playing an increasingly important role. we look forward to future research findings about 3-Bromo-5-nitropyridine.

Reference:
Patent; Hoffmann-La Roche Inc.; Hoves, Sabine; Wang, Lisha; Yun, Hongying; Zhang, Weixing; Zhu, Wei; (58 pag.)US2016/257653; (2016); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 109-04-6, In the chemical reaction process,reaction time,type of solvent,can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product.An updated downstream synthesis route of 109-04-6 as follows.

To a solution of 2-bromopyridine (XCIII) (10 g, 63 mmol, 1.00 eq) in THF (150 mL) was added n-BuLi (25.3 mL, 63 mmol, 1.00 eq) and the mixture was stirred at -70C for 30 mm under nitrogen atmosphere. Then n-Bu3SnCl (21.7 g, 67 mmol, 1.06 eq) was added and the mixture was stirred at the same temperature for another 2 h. Saturated ammonium chloride solution (150 mL) was added to the solution and extracted with EtOAc (150 mL x 3). The combined organic layers were dried over Na2504, filtered and concentrated in vacuo to afford the crude 2-(tributylstannyl)pyridine (XCIV) (25.9 g, 63 mmol, 100% yield) as a yellow oil. The crude product was used without further purification.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,109-04-6, its application will become more common.

Reference:
Patent; SAMUMED, LLC.; KC, Sunil Kumar; WALLACE, David Mark; CAO, Jianguo; CHIRUTA, Chandramouli; MARAKOVITS, Joseph Timothy; BOLLU, Venkataiah; HOOD, John; (307 pag.)WO2017/23989; (2017); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 1594-57-6 ,Some common heterocyclic compound, 1594-57-6, molecular formula is C6H7N3O, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.

General procedure: a) To a mixture of the carboxylic acid (5 mmol) in acetone (20 mL) was added EDC (5.5 mmol). The reaction mixture was stirred at room temperature for 30 min, then the amidoxime (5 mmol) was added. The resulting mixture was stirred at room temperature for 12 h. Acetone was evaporated at reduced pressure and to the residue was added water (100 mL). The resulting precipitate was filtered off, washed with water (50 ml) and dried under vacuum at rt.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,1594-57-6, its application will become more common.

Reference:
Article; Baykov, Sergey; Sharonova, Tatyana; Osipyan, Angelina; Rozhkov, Sergey; Shetnev, Anton; Smirnov, Alexey; Tetrahedron Letters; vol. 57; 26; (2016); p. 2898 – 2900;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 55304-73-9, Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps,and cheap raw materials. 55304-73-9, name is 2,6-Dichloro-3-formylpyridine. A new synthetic method of this compound is introduced below.

2,6-Dichloronicotinaldehyde (500 mg, 2.84 mmol) was diluted with dimethylamine (3125 muL, 6.25 mmol) and heated to 500C. After stirring for 3 hours, the reaction was loaded onto a silica gel column and eluted with 5% ethyl acetate/hexanes to 50% ethyl acetate/hexanes to yield 6-chloro-2-(dimethylamino)nicotinaldehyde (155 mg, 0.840 mmol, 29.6 % yield).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,55304-73-9, its application will become more common.

Reference:
Patent; ARRAY BIOPHARMA INC.; COOK, Adam; HUNT, Kevin, W.; DELISLE, Robert Kirk; ROMOFF, Todd; CLARK, Christopher, T.; KIM, Ganghyeok; CORRETTE, Christopher, P.; DOHERTY, George, A.; BURGESS, Laurence, E.; WO2010/75200; (2010); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 65515-28-8, name is Methyl 2,6-dichloronicotinate, the common compound, a new synthetic route is introduced below. Recommanded Product: 65515-28-8

A solution of 2,6-dichloronicotinic acid methyl ester (2.39 g, 11.6 mmol) and NaOMe (800 rog, 14.06 mmol) in THF (15 mL) was stirred at ambient temperature for 3 days. The reaction mixture was quenched by adding 10 mL of 10% NH4Cl solution and extracted with ether. The combined organic layers was dried over anhydrous Na2SO4 and concentrated to afford an unseparable mixture (1.7 g), containing 6-chloro-2-methoxynicotinic acid methyl ester.

The synthetic route of 65515-28-8 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; XENON PHARMACEUTICALS INC.; WO2006/14168; (2006); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem