Month: April 2022

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. 201937-23-7, name is 6-Chloronicotinimidamide hydrochloride. A new synthetic method of this compound is introduced below., name: 6-Chloronicotinimidamide hydrochloride

2-(6-chloropyridin-3-yl)-4-(2-methoxyethoxy)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (O-l) A suspension of 1-tert-butyl 3 -ethyl 4-oxopiperidine-l,3-dicarboxylate (A-I, 41.5 g, 153 mmol), -chloropyridine-S-carboximidamide hydrochloride (43.9 g, -85% pure, 194 mmol), and K2CO3 (59.8 g, 433 mmol) in DMF (457 mL) was treated with 2-bromoethyl methyl ether (26.3 ml, 280 mmol) with stirring. The mixture was heated to 65 ºC and stirred for 24 hr, adding additional small equivalents of 2-bromoethyl methyl ether and K2CO3 to drive reaction to completion if needed. The reaction mixture was diluted with EtOAc (1.5 L), and washed with water (2 L), sat. aq. NaHCO3 (2 L), water (2 L), and brine (1 L). The organic phase was dried over Na2SO4, filtered, and concentrated in vacuo to provide unpurified Boc-protected intermediate (~62 g), which was used in the subsequent step without further purification.

If you are interested in these compounds, you can also browse my other articles.Thank you for taking the time to read this article. I hope you enjoyed it, 201937-23-7, 6-Chloronicotinimidamide hydrochloride.

Reference:
Patent; MERCK SHARP &; DOHME CORP.; BRESLIN, Michael, J.; COLEMAN, Paul, J.; COX, Christopher, D.; RAHEEM, Izzat, T.; SCHREIER, John, D.; WO2010/138430; (2010); A1;,
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 160590-36-3, name is 2-Methoxy-3-nitro-4-methylpyridine. This compound has unique chemical properties. The synthetic route is as follows. name: 2-Methoxy-3-nitro-4-methylpyridine

BrSodium acetate (365 g, 5.37 mol) was added to a stirred solution of 2-methoxy-4-methyl-3-nitropyridine (250 g, 1.49 mol) in acetic acid (1.5 L) at ambient temperature, then bromine (639g, 4.00 mol) was added and the reaction was heated at 80 C for 12 h. The mixture was then quenched by the addition of 10% aqueous NaOH (1.5 L) and saturated aqueous Na2SO3 (1.5 L) at 0 C. The resulting solid was collected by filtration and washed with water, dried under vacuum to give the title compound (302 g, 82.2% yield) as a light yellow solid. ?H NMR (400MHz, DMSO-d6): oe 8.25 (s, 1 H), 3.94 (s, 3 H), 2.29 (s, 3 H).

With the rapid development of chemical substances, we look forward to future research findings about 160590-36-3.

Reference:
Patent; GENENTECH, INC.; CONSTELLATION PHARMACEUTICALS, INC.; ADLER, Marc; BURDICK, Daniel, J.; CRAWFORD, Terry; DUPLESSIS, Martin; MAGNUSON, Steven; NASVESCHUK, Christopher, G.; ROMERO, F. Anthony; TANG, Yong; TSUI, Vickie Hsiao-Wei; WANG, Shumei; (276 pag.)WO2016/123391; (2016); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 1227573-02-5, 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.1227573-02-5, name is 3-Bromo-5-fluoroisonicotinaldehyde, molecular formula is C6H3BrFNO, molecular weight is 204, as common compound, the synthetic route is as follows.

To a solution of 3-bromo-5-fluoroisonicotinaldehyde (5.0 g, 24.5 mmol, 1.0 eq) in DME (25.0 mL) was added Eta2 Eta220 (25.0 mL) and the reaction mixture was heated at 110 C overnight. After the reaction was complete, the solvent was concentrated. The resulting residue was diluted by water, extracted by EA (100.0 mL X 3), washed by brine, dried over Na2S04, concentrated. The resulting residue was purified by column chromatography (PE: EA = 2: 1) to provide 4-bromo-lH-pyrazolo[3,4-c]pyridine (1.5 g, 31.3%) as a white solid. LCMS (M+H+) m/z calculated 198.1, found 198.2.

The chemical industry reduces the impact on the environment during synthesis 1227573-02-5, I believe this compound will play a more active role in future production and life.

Reference:
Patent; LIFESCI PHARMACEUTICALS, INC.; MCDONALD, Andrew; QIAN, Shawn; (346 pag.)WO2018/11628; (2018); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 386704-06-9 , The common heterocyclic compound, 386704-06-9, name is 2-Chloro-6-(trifluoromethyl)nicotinonitrile, molecular formula is C7H2ClF3N2, 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.

2-Chloro-6-(trifluoromethyl)nicotinonitrile (340 mg, 1.65 mmol) was diluted with toluene (2.0 rnL), placed under nitrogen and cooled to -78C. DIBAL-H (3292 mul, 3.29 mmol) was added dropwise and the reaction was stirred for 1 hour. The reaction was warmed to 00C and acetic acid (1 mL) was added followed by 5 mL of water. After stirring for 2 hours, the reaction was extracted twice with ethyl acetate, washed with Rochelle’s salt, dried over MgSO4, filtered and concentrated. The material was loaded onto silica gel and eluted with 5% ethyl acetate/hexanes to 30% ethyl acetate/hexanes to yield the desired compound(115 mg, 0.549 mmol, 33.3 % yield) as a clear oil.

The synthetic route of 386704-06-9 has been constantly updated, and we look forward to future research findings.

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

Electric Literature of 57963-08-3, Adding some certain compound to certain chemical reactions, such as: 57963-08-3, name is 5,6-Dimethylpyridin-2-amine,molecular formula is C7H10N2, 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 57963-08-3.

Step 1 Ethyl 6-chloro-4-(5,6-dimethylpyridin-2-ylamino)pyridazine-3-carboxylate A heavy walled sealable tube was charged with ethyl 4,6-dichloropyridazine-3-carboxylate (300 mg, 1.36 mmol) and 5,6-dimethylpyridin-2-amine (249 mg, 2.04 mmol). To the mixture was added acetonitrile (8.00 mL) and the reaction mixture was heated with stirring in an oil bath at 140 C. for 20 h. After cooling to room temperature the residue was suspended in dichloromethane and purified by flash chromatography (silica 20-45 muM, 40 g, Thomson) eluting with 0 to 10% over 20 min, acetone/dichloromethane to give ethyl 6-chloro-4-(5,6-dimethylpyridin-2-ylamino)pyridazine-3-carboxylate (195 mg, 46.8%) as an off-white solid. 1H NMR (CHLOROFORM-d) delta: 10.54 (s, 1H), 9.14 (s, 1H), 7.41 (d, J=8.3 Hz, 1H), 6.70 (d, J=8.3 Hz, 1H), 4.55 (q, J=7.2 Hz, 2H), 2.50 (s, 3H), 2.26 (s, 3H), 1.50 (t, J=7.2 Hz, 3H); LC-MS 307.0 [M+H]+.

According to the analysis of related databases, 57963-08-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Hoffman-La Roche Inc.; Hermann, Johannes Cornelius; Kennedy-Smith, Joshua; Lucas, Matthew C.; Padilla, Fernando; Soth, Michael; US2013/178478; (2013); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Related Products of 628691-93-0, 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 628691-93-0, name is 2-Chloro-3-fluoroisonicotinic acid. This compound has unique chemical properties. The synthetic route is as follows.

Diphenylphosphoryl azide (DPPA) (129 mmol) wasadded to a mixture of 2-chloro-3-fluoro-pyridine-4-carbox- ylic acid (85.7 mmol), Et3N (257 mmol) in 1:1 tert-l3uOH/ toluene (200 mE). The mixture was heated at 110 C. for 4 h. Mixture was diluted with H20 and extracted with DCM. The organic layer was dried (Na2504) and concentrated. The residue was purified by flash column chromatography (5i02, 100:0 to 80:20 DCM/EtOAc) to yield the desired product tert-butyl N-(2-chloro-3-fluoro-4-pyridyl)carbamate.

While traditionally a conservative industry, chemical producers will need to modernize their PR strategies to stay relevant.we look forward to future research findings about 628691-93-0, 2-Chloro-3-fluoroisonicotinic acid.

Reference:
Patent; GALAPAGOS NV; Menet, Christel Jeanne Marie; Mammoliti, Oscar; Blanc, Javier; Orsulic, Mislav; Roscic, Maja; (81 pag.)US9440929; (2016); B2;,
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. 77837-09-3, name is Methyl 6-oxo-1-phenyl-1,6-dihydropyridine-3-carboxylate, the common compound, a new synthetic route is introduced below. HPLC of Formula: C13H11NO3

Step 3; 6-Oxo-l -phenyl- 1 ,6-dihydropyridine-3-carboxylic acid:; Lithium hydroxide monohydrate (0.366 g, 8.73 mmol) was added to a mixture of methyl-6-oxo-l -phenyl- 1,6- dihydropyridine-3-carboxylate (1.0 g, 4.37 mmol), tetrahydrofuran (9 mL) and water (6 mL) at 0 °C. The mixture was stirred for 1 hour, diluted with water and washed with ethyl acetate. The pH of the aqueous layer was adjusted to 2 using 2 N hydrochloric acid and the precipitate was filtered to give the title compound as a brown solid (0.740 g, 79percent). m.p. 256-263 °C; *H NMR (400 MHz, DMSO-d6) delta 6.53 (d, / = 9.4 Hz, 1H), 7.40-7.49 (m, 5H), 7.87 (dd, / = 2.5, 9.8 Hz , 1H), 8.23 (d, / = 2.5 Hz, 1H); IR (KBr) upsilon 3446, 1708, 1645, 1577, 1263, 1228 cm”1; MS 214 (M – 1).

The synthetic route of 77837-09-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AUSPEX PHARMACEUTICALS, INC.; ZHANG, Chengzhi; SOMMERS, Andreas; WO2012/122165; (2012); A2;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 1228631-54-6, 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. 1228631-54-6, name is 1-(6-(Trifluoromethyl)pyridin-3-yl)ethanol, molecular formula is C8H8F3NO, 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.

Example 69: Preparation of Carbamates – General Method AThe acyl azide was suspended in dry toluene (0.35 M). To the resulting slurry was added the appropriate alcohol (1.20 equiv). The slurry was heated to 100 0C (external) for 4-24 h and then cooled to ambient temperature. The product was isolated by vacuum filtration or purified by silica gel column chromatography (after applying the material directly to the column) eluting with EtOAc/hexanes gradient. In some instances, further purification by recrystallization was necessary. Typical solvents used include: chloroform-Patent; DOW AGROSCIENCES LLC; LAMBERT, William; CROUSE, Gary; SPARKS, Thomas; CUDWORTH, Denise; WO2011/17513; (2011); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 915006-52-9, 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.915006-52-9, name is 6-Bromo-2-iodopyridin-3-amine, molecular formula is C5H4BrIN2, molecular weight is 298.91, as common compound, the synthetic route is as follows.

To a mixture of 6-bromo-2-iodopyridin-3-amine (100 mg, 0.34 mmol), 1,2-dimethoxy-4-(prop-1-yn-1-yl)benzene (74 mg, 0.42 mmol), lithium chloride (18 mg, 0.42 mmol), sodium carbonate (180 mg, 1.68 mmol) and Pd(dppf)Cl2 (12.5 mg, 0.017 mmol) in a screw cap vial was added DMF (2 mL). The vial was fitted with a Teflon-lined septum cap. The system was evacuated under vacuum (via a needle from a nitrogen/vacuum manifold line) and backfilled with nitrogen gas. The procedure was repeated three times. The needle was removed and the vial was heated at 100 C. for 16 h. LCMS analysis shows formation of two isomers, in approximately 3:1 ratio. 1H NMR analysis suggested the major product to be 5-bromo-2-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrrolo[3,2-b]pyridine (5A-1). The reaction mixture was diluted with EtOAc (50 mL), poured into a separatory funnel and washed with 10% aqueous LiCl solution (2*10 mL) and saturated aqueous NaCl solution (10 mL), dried (Na2SO4), filtered and the filtrate was concentrated. The crude product was dissolved in a small amount of DCM and purified on a silica gel column chromatography with a 15 min gradient from 0%-100% DCM/EtOAc to afford 5-bromo-2-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrrolo[3,2-b]pyridine (Intermediate 5A-1) that was contaminated with Intermediate 5A-2, 5-bromo-3-(3,4-dimethoxyphenyl)-2-methyl-1H-pyrrolo[3,2-b]pyridine, m/z (303, M+1), 80 mg (67%). To a mixture containing 5-bromo-2-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrrolo[3,2-b]pyridine (Intermediate 5A-1) and Intermediate 5A-2 (100 mg, 0.29 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1 (2H)-carboxylate (111 mg, 0.36 mmol), and Pd(dppf)C12 (10.5 mg, 0.014 mmol) in a screw cap vial was added THF (2.5 mL) followed by 3M aqueous solution of tripotassium phosphate (0.10 mL, 0.3 mmol). The vial was fitted with a Teflon lined septum cap. The system was evacuated under vacuum (via a needle from a nitrogen/vacuum manifold line) and backfilled with nitrogen gas. The procedure was repeated three times. The needle was removed and the vial was heated at 75 C. for 3 h. The reaction mixture was cooled to room temperature and treated with saturated aqueous NaCl solution (5 mL) and extracted with ethyl acetate (3*10 mL). The extracts were combined, dried (Na2SO4), filtered and concentrated. The crude product was dissolved in a small amount of DCM and purified on silica gel column chromatography eluting with a 10 min gradient from 5%-100% DCM/EtOAc. No separation was observed. A mixture of tert-butyl 4-(2-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate (Intermediate 5B) and the regioisomer tert-butyl 4-(3-(3,4-dimethoxyphenyl)-2-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-5,6-dihydropyridine-1 (2H)-carboxylate was isolated (100 mg, 77% yield), m/z (550, M+1) and was used as such in subsequent step. A mixture of tert-butyl 4-(2-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate (Intermediate 5B) and regioisomer tert-butyl 4-(3-(3,4-dimethoxyphenyl)-2-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate (95 mg, 0.21 mmol) was dissolved in MeOH (5 mL) and transferred to a Parr bottle. The mixture was purged with nitrogen. Pearlman’s Catalyst (25 mg, 0.036 mmol) was added and the bottle was pressurized with hydrogen gas (50 psi) and shaken for 22 h. The reaction mixture was filtered through a pad of Celite and the filtrate was concentrated. The resulting residue was dissolved in a small amount of DCM and charged to a silica gel column, which was eluted over a 10 min gradient with 1%-5% MeOH/DCM to afford a mixture of tert-butyl 4-(2-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate (Intermediate 5C) and the regioisomer tert-butyl 4-(3-(3,4-dimethoxyphenyl)-2-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)-5,6-dihydropyridine-1 (2H)-carboxylate (82 mg, 80%), m/z (452, M+H). The mixture of isomers (tert-butyl 4-(2-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)piperidine-1-carboxylate (Intermediate 5C) and tert-butyl 4-(3-(3,4-dimethoxyphenyl)-2-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)piperidine-1-carboxylate (80 mg, 0.18 mmol) were suspended in 4 N HCl in dioxane (4 mL, 16.00 mmol), stirred for 30 min, and concentrated to dryness. The resulting residue was suspended in diethyl ether (1 mL) and the solids were filtered and dried to give a mixture of 2-(3,4-dimethoxyphenyl)-3-methyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridine (Intermediate 5D) and 3-(3,4-dimethoxyphenyl)-2-methyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridine as bis HCl salts (50 mg, 65%), m/z (352, M+H). To a solution containing a mixture of 3-(3,4-dimethoxyphenyl)-2-methyl-5-(piperidin-4-yl)-1H-pyrrolo[2,3-c]pyridine 2 HCl (Intermediate 5D) and 2-(3,4-dimethoxyphenyl)-3-methyl-5-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridine, 2 HCl (30 mg, 0.07 mmol) in DMF (1 mL) was added 1-isobu…

Statistics shows that 915006-52-9 is playing an increasingly important role. we look forward to future research findings about 6-Bromo-2-iodopyridin-3-amine.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; Dyckman, Alaric J.; Dodd, Dharmpal S.; Mussari, Christopher P.; Sherwood, Trevor C.; Whiteley, Brian K.; Gilmore, John L.; Kumar, Sreekantha Ratna; Pasunoori, Laxman; Srinivas, Pitani Veera Venkata; Duraisamy, Srinivasan Kunchithapatham; Hegde, Subramanya; Anumula, Rushith Kumar; US2019/185469; (2019); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 863704-60-3, 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.863704-60-3, name is 6-(4-Fluorophenyl)picolinic acid, molecular formula is C12H8FNO2, molecular weight is 217.2, as common compound, the synthetic route is as follows.

A mixture of Intermediate 3-07 (156 mg, 0.72 mmol), HATU (394 mg, 1.0 mmol) and DIPEA (0.639 mL, 3.66 mmol) in DCM (6 mL) was stirred at RT for 15 min. A solution of Intermediate 3-04 (155 mg, 0.72 mmol) in DCM (4 mL) was added and the reaction mixture was stirred at RT for 14 h. The mixture was washed with water, and the organic layer was dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography (Biotage, cHex:EtOAc, 85:15 to 50:50) to afford Intermediate 3-09 (298 mg, 100%).

Statistics shows that 863704-60-3 is playing an increasingly important role. we look forward to future research findings about 6-(4-Fluorophenyl)picolinic acid.

Reference:
Patent; CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS (CNIO); PASTOR FERNANDEZ, Joaquin; ALVAREZ ESCOBAR, Rosa Maria; GARCIA GARCIA, Ana Belen; RIESCO FAGUNDO, Rosario Concepcion; BLANCO APARICIO, Carmen; WO2012/98387; (2012); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem