Day: April 12, 2022

Synthetic Route of 1231930-13-4, Adding some certain compound to certain chemical reactions, such as: 1231930-13-4, name is 3-Bromo-2-methyl-6-nitropyridine,molecular formula is C6H5BrN2O2, 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 1231930-13-4.

A mixture of Example C6 (2 g, 5.15 mmol), Example A6 (1.053 g, 3.96 mmol) and Pd(PPh3)4 (0.229 g, 0.198 mmol) in toluene (20 mL), sparged with Ar and heated at 105 C. overnight. The mixture was cooled to RT, treated 10% KF (aq) and EtOAc and stirred at RT for 2 h. The solids were removed via filtration through diatomaceous earth, washed with EtOAc and the filtrate was washed with satd. NaHCO3, then brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (EtOAc/Hex) to afford 2-methyl-5-(4-((2-methyl-6-nitropyridin-3-yl)oxy)pyridin-2-yl)thiazole (1.06 g, 81%). 1H NMR (400 MHz, DMSO-d6): delta 8.50 (d, J=5.7 Hz, 1H), 8.34 (s, 1H), 8.24 (d, J=8.7 Hz, 1H), 7.88 (d, J=8.7 Hz, 1H), 7.72 (d, J=2.4 Hz, 1H), 7.02 (dd, J=5.7, 2.4 Hz, 1H), 2.65 (s, 3H), 2.50 (s, 3H); MS (ESI) m/z: 329.1 (M+H+).

According to the analysis of related databases, 1231930-13-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Deciphera Pharmaceuticals, LLC; Flynn, Daniel L.; Kaufman, Michael D.; Samarakoon, Thiwanka; Caldwell, Timothy Malcolm; Vogeti, Lakshminarayana; Ahn, YuMi; Patt, William C.; Yates, Karen M.; US2014/315917; (2014); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 145255-19-2, 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. 145255-19-2, name is 5-Aminopyridine-2-carboxamide, molecular formula is C6H7N3O, 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 a stirring slurry of 5-aminopyridine-2-carboxamide (47 mg, 0.35 mmol) in dichloromethane (1 mL) and DIEA (80 mu, 0.46 mmol) at 0 C was added a slurry of cold 2-fluoro-6-[2- (trideuteriomethoxy)-4-(trifluoromethoxy)phenoxy]-4-(trifluoromethoxy)benzoyl chloride (104 mg, 0.230 mmol) in dichloromethane (1 mL) dropwise. The reaction mixture was removed from ice bath after 10 minutes and stirred at room temperature for 18 hours. The reaction was concentrated in vacuo and purified by HPLC (10-99% acetonitrile/5 mM HCl) to provide 5-[[2-fluoro-6-[2-(trideuteriomethoxy)-4- (trifluoromethoxy)phenoxy]-4-(trifluoromethoxy)benzoyl]amino]pyridine-2-carboxamide (24 mg, 19%). ESI-MS m/z calc. 552.10, found 552.9 (M+l)+; retention time (Method C): 2.57 minutes. NMR (400 MHz, DMSO-d6) delta 11.26 (s, 1H), 8.84 (s, 1H), 8.26 (dd, J = 8.7, 2.5 Hz, 1H), 8.07 – 7.95 (m, 2H), 7.55 (s, 1H), 7.43 – 7.25 (m, 2H), 7.21 (d, J = 2.8 Hz, 1H), 7.08 – 6.93 (m, 1H), 6.56 (s, 1H) ppm.

According to the analysis of related databases, 145255-19-2, the application of this compound in the production field has become more and more popular.

Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; AHMAD, Nadia; ANDERSON, Corey; ARUMUGAM, Vijayalaksmi; ASGIAN, Iuliana, Luci; CAMP, Joanne, Louise; FANNING, Lev Tyler, Dewey; HADIDA RUAH, Sara, Sabina; HURLEY, Dennis; SCHMIDT, Yvonne; SHAW, David; SHETH, Urvi, Jagdishbhai; THOMSON, Stephen, Andrew; (691 pag.)WO2019/14352; (2019); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 915006-52-9 ,Some common heterocyclic compound, 915006-52-9, molecular formula is C5H4BrIN2, 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.

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).

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles. 915006-52-9, 6-Bromo-2-iodopyridin-3-amine, other downstream synthetic routes, hurry up and to see.

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

Related Products of 1231930-13-4, 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. 1231930-13-4, name is 3-Bromo-2-methyl-6-nitropyridine. A new synthetic method of this compound is introduced below.

2-(4-methyl-1H-imidazol-1-yl)pyridin-4-ol (200 mg, 1.14 mmol) was dissolved in N,N-dimethylformamide (5 mL), and then 3-bromo-2-methyl-6-nitropyridine (250 mg, 1.14 mmol), and potassium carbonate (472 g, 3.42 mmol) were added. The reaction solution was stirred at 90 C. for 16 hrs, then poured into water (200 mL), and then extracted twice with ethyl acetate (50 mL*2). The organic phases were combined and washed once with a brine (100 mL), dried over sodium sulfate, then concentrated, and separated by column chromatography (eluent: petroleum etherpetroleum ether/ethyl acetate (4:6)) to obtain 2-methyl-3-((2-(4-methyl-1H-imidazol-1-yl)pyridin-4-yl)oxy)-6-nitropyridine (60 mg, yield 17%). MS m/z (ESI): 311 [M+H]+

At the same time, in my other blogs, there are other synthetic methods of this type of compound,1231930-13-4, 3-Bromo-2-methyl-6-nitropyridine, and friends who are interested can also refer to it.

Reference:
Patent; Abbisko Therapeutics Co., Ltd.; ZHAO, Baowei; ZHANG, Mingming; YU, Hongping; YANG, Shuqun; CHEN, Zhui; XU, Yaochang; US2020/71302; (2020); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

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.5832-43-9, name is 4-Methyl-5-nitropicolinic acid, molecular formula is C7H6N2O4, molecular weight is 182.13, as common compound, the synthetic route is as follows.Formula: C7H6N2O4

To a solution of 4-methyl-5-nitro-2-pyridinecarboxylic acid (1.0 g, 5.5 mmol) in methanol (50 mL) was added concentrated HQ (8 mL, 97 mmol) at room temperature. The mixture was heated at reflux for 18h, then cooled to room temperature. The crude mixture was partitioned between EtOAc and saturated NaHCO3 and the aqueous layer was extracted with EtOAc (twice). The combined organic phase was washed with brine, dried over anhydrous MgS0 , filtered and concentrated to provide methyl 4-methyl-5-nitropicolinate. -NMR (CDC13, 500 MHz), delta 9.23 (s, 1H), 8.16 (s, 1H), 4.06 (s, 3H), 2.77 (s, 3H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound,5832-43-9, 4-Methyl-5-nitropicolinic acid, and friends who are interested can also refer to it.

Reference:
Patent; MERCK SHARP & DOHME CORP.; WALSH, Shawn, P.; CATO, Brian; FRIE, Jessica, L.; KIM, Dooseop; PASTERNAK, Alexander; SHI, Zhi-Cai; WO2014/85210; (2014); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Related Products of 73112-16-0, Adding some certain compound to certain chemical reactions, such as: 73112-16-0, name is 2,6-Dibromo-4-methylpyridine,molecular formula is C6H5Br2N, 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 73112-16-0.

To a solution of 2,6-dibromo-4-methyl-pyridine (5.1 g, 20.4 mmol) and 4-[l-(4-Methoxy-benzyl)-l H-pyrazol-4-yl]-pyridin-2-ylamine (5.2 g, 18.6 mmol) in dioxane (150 mL) was added sodium tert-butoxide (1.96 g, 20.4 mmol) and then l, l ‘-bis(di-t- butylphosphino)ferrocene palladium dichloride (1.2 g, cat.) was added. The mixture was degassed by nitrogen for 3 times and then refluxed for 15h. The mixture was partitioned between water and EtOAc, and the organic layers were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified via flash- chromatography on silica gel (30 % EtOAc in petroleum ether) to give (6-Bromo-4-methyl- pyridin-2-yl)- {4-[l-(4-methoxy-benzyl) -lH-pyrazol-4-yl]-pyridin-2-yl}-amine (3.0 g, yield 36.1 %) as a light yellow solid. MS ESI calc’d. For: C22 H20BrN5O [M + H]+ 450, found 450.

According to the analysis of related databases, 73112-16-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MERCK SHARP & DOHME CORP.; ANDRESEN, Brian, M.; ANTHONY, Neville, J.; MILLER, Thomas, A.; WO2014/74422; (2014); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 79491-46-6 ,Some common heterocyclic compound, 79491-46-6, molecular formula is C6H4Br2N2O3, 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.

To a solution of Compound 138 (200 mg, 0.64 mmol) in anhyd MeOH (6 mL) was added NaOMe (46 mg, 0.85 mmol). The reaction mixture was stirred at room temperature for 1 h and then concentrated under vacuum. The resulting residue was washed with water and filtered. The collected solids were washed with ice cold water and dried under vacuum to give Compound 139 (150 mg, 89% yield).

In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles. 79491-46-6, 2,6-Dibromo-3-methoxy-5-nitropyridine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; EXELIXIS, INC.; BANNEN, Lynne Canne; BUI, Minna; JIANG, Faming; WANG, Yong; XU, Wei; (235 pag.)WO2019/148043; (2019); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Adding a certain compound to certain chemical reactions, such as: 62150-47-4, Ethyl 4-bromopicolinate, 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, 62150-47-4, blongs to pyridine-derivatives compound. Product Details of 62150-47-4

A solution of ethyl 4-bromo-2-picolinate (1e) (92%, 20.6 g, 82.3 mmol) and acetone (2.43 mL, 32.9 mmol) in DME (100 mL) was added dropwise to a stirred suspension of NaH (60% suspension in oil, 6.6 g, 165 mmol) in DME (100 mL) under an atmosphere of argon at room temperature. The temperature was slowly increased until reflux was achieved, and a vigorous evolution of gas was observed after 10 min and the brown suspension turned dark red. The reaction mixture was allowed to cool to room temperature and was stirred for 2 h. The solvent was removed in vacuo and the red-orange paste slowly treated with water (200 mL). The resultant insoluble mixture was acidified as described in previously to pH 6.5 and the copious amount of yellow solid so obtained was collected by filtration and washed with water until the washing appeared colourless. The solid was oven-dried under vacuum (40C, ca. 30 mm) for 2 days to yield the crude triketone 5e as a yellow solid (15.3 g).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,62150-47-4, its application will become more common.

Reference:
Article; Lin, Chih-Pei; Florio, Pas; Campi, Eva M.; Zhang, Chunfang; Fredericks, Dale P.; Saito, Kei; Jackson, W. Roy; Hearn, Milton T.W.; Tetrahedron; vol. 70; 45; (2014); p. 8520 – 8531;,
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 26956-43-4, name is Furo[3,2-c]pyridin-4(5H)-one. This compound has unique chemical properties. The synthetic route is as follows. Safety of Furo[3,2-c]pyridin-4(5H)-one

Preparation 20; 7-Bromofuro [3,2-c] pyridine; 7-Bromo-5H-furoF3, 2-clpyn; Add N-bromosuccinimide (63.16 g, 354.9 mmol) as a solution in anhydrous acetonitrile (480 mL) to a suspension of 5H-furo [3,2-c] pyridin-4-one (36.9 g, 273 mmol) in anhydrous acetonitrile (740 mL) at 0 C over 1 hour. Warm to room temperature, add anhydrous methyl alcohol (1.5 L) and stir at room temperature for 18 hours. Quench with water (20 ml) and saturated sodium bicarbonate (20 mL), concentrate to a volume of 1.3 liters, and pour into water (1.3 L). Collection of the precipitate by filtration and drying (vacuum oven 2 days 40-60 C) gives the title compound as an off-white solid. ESMS: (m/z) = 213.9, 215.9 (M++1).

With the rapid development of chemical substances, we look forward to future research findings about 26956-43-4.

Reference:
Patent; ELI LILLY AND COMPANY; WO2003/76442; (2003); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Related Products of 1086381-43-2 ,Some common heterocyclic compound, 1086381-43-2, molecular formula is C8H10BrN, 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.

Step 4: To a vial containing palladium(II) acetate (4.3 mg, 0.019 mmol) and butyldi-1-adamantylphosphine (13.9 mg, 0.039 mmol) was added 1,4-dioxane (300 ul). The vial was evacuated and refilled with Ar (3*). The solution was warmed to 70 C. for 20 minutes. In a separate vial were combined pivalic acid (9.9 mg, 0.097 mmol), cesium fluoride (44 mg, 0.29 mmol), 2-bromo-4-isopropylpyridine (purchased from CombiPhos Catalysts, Inc.) (29 mg, 0.15 mmol), (R)-4-((1-cyclobutylethyl)amino)-7-methyl-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile (40 mg, 0.097 mmol) and 1,4-dioxane (0.5 mL). The mixture was degassed with Ar for 15 minutes, and the catalyst solution was added to the mixture. The resulting mixture was stirred at 130 C. for 3 days. The mixture was cooled to room temperature and concentrated. The residue was dissolved in DCM and purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient) to give (R)-4-((1-cyclobutylethyl)amino)-2-(4-isopropylpyridin-2-yl)-7-methyl-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc’d for C30H31F3N6 [M+H]+ 533. found 533.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,1086381-43-2, its application will become more common.

Reference:
Patent; Christopher, Matthew P.; Fradera Llinas, Francesc Xavier; Machacek, Michelle; Martinez, Michelle; Reutershan, Michael Hale; Shizuka, Manami; Sun, Binyuan; Thompson, Christopher Francis; Trotter, B. Wesley; Voss, Matthew E.; Altman, Michael D.; Bogen, Stephane L.; Doll, Ronald J.; US2014/179680; (2014); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem