Month: April 2022

Reference of 327056-62-2 ,Some common heterocyclic compound, 327056-62-2, molecular formula is C6H3FN2, 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) 2-[(5-Fluoropyridine-2-carbonyl)amino]malonic acid diethyl ester A 6 N aqueous solution of hydrochloric acid (100 mL) containing the 5-fluoropyridine-2-carbonitrile (11.8 g) was heated to reflux for 4 hours. After air cooling, Nacl was added to the reaction solution for saturation, and ethyl acetate was further added thereto. The resultant mixture was partitioned, and the organic layer was dried over anhydrous sodium sulfate. After separating the organic layer by filtration, the solvent was evaporated under reduced pressure, and a residue thus obtained was dissolved in N,N-dimethylformamide (140mL). Then, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (6.0 g), 1-hydroxybenzotriazole (770mg), and aminomalonic acid diethyl ester hydrochloride (7.2 g) were added to the solution, and the resultant mixture was stirred at room temperature for 19.5 hours. Water and ethyl acetate were added to the reaction solution, and the mixture was partitioned. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate. After separating the organic layer by filtration, the solvent was evaporated under reduced pressure, and a residue thus obtained was purified by silica gel column chromatography (hexane-ethyl acetate), to obtain 2-[(5-fluoropyridine-2-carbonyl)amino]malonic acid diethyl ester (9.4 g, 53%) as a solid. 1H-NMR (400MHz, CDCl3) delta: 1.33 (6H, t, J=7.1Hz), 4.27-4.38 (4H, m), 5.36 (1H, d, J=7.4Hz), 7.51-7.56 (1H, m), 8.20-8.21 (1H, m), 8.46 (1H, d, J=2.7Hz), 8.74 (1H, d, J=10.0Hz).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,327056-62-2, its application will become more common.

Reference:
Patent; DAIICHI PHARMACEUTICAL CO., LTD.; EP1803719; (2007); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Related Products of 153747-97-8, 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 153747-97-8, name is tert-Butyl 4-(5-bromopyridin-2-yl)piperazine-1-carboxylate. This compound has unique chemical properties. The synthetic route is as follows.

To a solution of tert -butyl 4-(5-bromopyridin-2-yl)piperazine-l-carboxylate (250 mg, 0.730 mmol) in 2.5 mL anhydrous THF was added 2.5 M w-butyllithium (320 muL, 0.80 mmol) at -78 0C under nitrogen atmosphere. After stirring for 45 mins, the reaction mixture was charged with dimethyl phosphinic chloride (164.4 mg, 1.46 mmol) in 1 mL anhydrous THF. The reaction mixture was warmed to -30 0C over 3 h. The mixture was quenched with saturated ammonium chloride aqueous solution and the mixture was partitioned between DCM and brine. The organic layer was dried over Na2SO4 and concentrated to afford the crude material. The resulting solid was purified by flash chromatography on silica gel, eluting with 20 – 100% EtOAc : heptane. Fractions containing the desired product were combined and concentrated to afford an off white solid (100 mg, 40.3% yield). The Boc protected title compound was dissolved in 2-PrOH (1 mL) and charged with 4 N HCl. The reaction mixture was heated at 70 0C for 30 min, and concentrated to afford the titled product as a HCl salt. MS (m/z, MH+): meas. 240.2 calc. 240.3

According to the analysis of related databases, 153747-97-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; NOVARTIS AG; WO2008/110611; (2008); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 135450-23-6 ,Some common heterocyclic compound, 135450-23-6, molecular formula is C7H5ClN2, 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 commercially available chloride 30 (9.66 g,63.3 mmol) in DMF (400 mL) at ambient temperature was treatedwith potassium phthalimide (11.7 g, 63.3 mmol). After stirring for5 h, the mixture was concentrated under vacuum. The remainingmixture was taken up in H2O (200 mL) and was filtered to collectthe solid. The solid was washed with H2O (100 mL) and THF(100 mL) to obtain the desired phthalimide derivative (11.5 g,69%) and was moved forward without further purification. To asolution of the crude phthalimide derivative (5.84 g, 22.2 mmol)in THF/MeOH (200 mL, 1:1, v/v) at ambient temperature was treatedwith hydrazine monohydrate (1.18 mL, 24.4 mmol). After 2 h,1.0 M HCl (24.5 mL) was added to the mixture and was stirredfor another 3 h before concentrating the reaction mixture undervacuum. The remaining residue was taken up in H2O (200 mL)and the unwanted solid was removed through filtration. The filtratewas concentrated and placed under vacuum to remove theremaining H2O. The crude solid was taken up in CH2Cl2 (175 mL)and triethylamine (9.28 mL, 66.6 mmol) and Boc2O (4.86 g,24.4 mmol) was added. After stirring for 12 h at room temperature,the reaction was quenched with a saturated solution of NaHCO3(200 mL), extracted with CH2Cl2 (3 150 mL), dried over MgSO4,and concentrated under reduced pressure. The residue was purifiedusing flash chromatography (10-45% ethyl acetate in hexanes)to provided the aryl pyridine ?IN? fragment (2.24 g, 43%): 1H NMR(CDCl3, 400 MHz) d 7.78 (t, J = 7.6 Hz, 1H), 7.56 (d, J = 7.6 Hz, 1H),7.49 (d, J = 8.0 Hz, 1H), 5.51 (s, 1H), 4.44 (d, J = 5.6 Hz, 2H), 1.43(s, 9H); 13C NMR (CDCl3, 100 MHz) 160.1, 155.9, 137.6, 133.0,127.0, 125.1, 117.1, 79.9, 45.5, 28.3; IR (neat) 3347, 2979, 2934,2239, 1699, 1518, 1453, 1250, 1170, 862; HRMS (ESI) m/z calcdfor C12H15N3NaO3 [M+Na]+ 256.1062, found 256.1062.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,135450-23-6, its application will become more common.

Reference:
Article; Clausen, Dane J.; Smith, William B.; Haines, Brandon E.; Wiest, Olaf; Bradner, James E.; Williams, Robert M.; Bioorganic and Medicinal Chemistry; vol. 23; 15; (2015); p. 5061 – 5074;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 23628-31-1 ,Some common heterocyclic compound, 23628-31-1, molecular formula is C6H6N2O2, 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 2-amino-6-pyridinecarboxylic acid (6.0 g, 43.5 mmol) in ethanol (150 mL) was added thionyl chloride (12.0 g, 101 mmol) at 0 C. The resulting reaction mixture was stirred at reflux for 12 h. Upon cooling to room temp, the reaction mixture was concentrated under reduced pressure. Saturated aqueous Na2CO3 solution was added until the pH of the solution reached 9. The mixture was concentrated under reduced pressure and dichloromethane (150 mL) was added to the resulting residue. The mixture was stirred vigorously at room temp for 30 min and then filtered. The filtrate was concentrated under reduced pressure to afford ethyl 6-aminopicolinate (5.5 g, 76 % 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. 23628-31-1, 6-Aminopicolinic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; GlaxoSmithKline LLC; CASAUBON, Rebecca, L.; NARAYAN, Radha; OALMANN, Christopher; VU, Chi, B.; (583 pag.)EP2768509; (2017); B1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 179687-79-7, 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 179687-79-7 as follows.

Step B: 3-chloro-4-(2-pyridylmethoxyl)-phenylamine (compound 8.2)[0125] 2.65g of compound 8.1 (lOmmol) was suspended in MeOH (50 ml) and treated wet 5% Pt/C (Degussa type, Aldrich, 1.5 g). The flask is flushed with hydrogen gas from a balloon and the reaction mixture was stirred under hydrogen balloon for 2 hours. The reaction mixture was filtered through a Celite plug and the solvent is removed under reduced pressure to yield 2.0 g of the desired product.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,179687-79-7, its application will become more common.

Reference:
Patent; KANIONUSA INC.; SHEN, Wang; ZHANG, Aimin; FAN, Junfa; ZHENG, Xiaoling; WO2011/2523; (2011); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 107351-82-6, 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.107351-82-6, name is 2-Bromo-5-phenylpyridine, molecular formula is C11H8BrN, molecular weight is 234.09, as common compound, the synthetic route is as follows.

Synthesis of Intermediate 14-B: Under nitrogen, in 250ml three-neck round bottom flask, Intermediate 14-A (7.02g, 0.03mol), and 120ml dried THF that underwent treatment with by Na / benzophenone were added. Liquid nitrogen was used to cool to -78C, then slowly added dropwise with stirring 14.5ml of n-butyllithium (0.036mol, 2.5mol·L-1), triisopropyl borate 9.96ml (8.12g, 0.043mol). After stirring to room temperature. Addition of an appropriate amount of dilute hydrochloric acid was added, extracted with ethyl acetate,The combined organic phases, the organic solvent was removed by rotary evaporation to give the crude product. And through recrystallization from ethanol as a white solid 3.92g, yield 65.7%.

Statistics shows that 107351-82-6 is playing an increasingly important role. we look forward to future research findings about 2-Bromo-5-phenylpyridine.

Reference:
Patent; Kunshan Visionox Display Co., Ltd.; Tsinghua University; Beijing Weixinnuo Science And Technology Co., Ltd.; Qiu, Yong; Liu, Fei; Li, Yinkui; (36 pag.)CN102977129; (2016); B;,
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.896722-51-3, name is 6-Methyl-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine, molecular formula is C14H12N2O2S, molecular weight is 272.32, as common compound, the synthetic route is as follows.Quality Control of 6-Methyl-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine

A solution of 50% NaOH (0.573 g) was added to N-protected 6-methyl-7-azaindole (0.390 g, 1.43 mmol) in Ethanol (10 mL). After refluxed for 8 h, the mixture was concentrated and was extracted with CHCl3. The organic layer was washed with water and dried. The solvent was evaporated in vacuo and the residue was purified on a silica gel column eluting with EtOAc/hexane (1:3) to give 6-methyl-1H-pyrrolo[2,3-b]pyridine (0.148 g, 78%).

At the same time, in my other blogs, there are other synthetic methods of this type of compound,896722-51-3, 6-Methyl-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine, and friends who are interested can also refer to it.

Reference:
Patent; Hsieh, Hsing-Pang; Chao, Yu-Sheng; Liou, Jing-Ping; Chang, Jang-Yang; Tung, Yen-Shih; US2006/148801; (2006); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Adding a certain compound to certain chemical reactions, such as: 134363-45-4, 2-(Pyridin-3-yl)benzoic acid, 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, Computed Properties of C12H9NO2, blongs to pyridine-derivatives compound. Computed Properties of C12H9NO2

A mixture of [2-[4-(4-amino-2-fluoro-phenyl)-piperazin-1 -yl]-lambda/-ethyl-2- phenyl-acetamide (320 mg, 0.90 mmol), 2-(3′-pyridyl) benzoic acid (200 mg, 0.99 mmol) and HATU (375 mg, 0.99 mmol) in DMF (10 ml_) was treated with DIPEA (170 mul_, 0.99 mmol) and let stir at room temperature for 6 h. The reaction mixture was quenched with H2O and extracted with EtOAc. The organic layer was separated and washed (sat’d NaHCO3, brine), dried (Na2SO4), filtered and concentrated to yield a semi solid, which was purified by PTLC (5% 2M NH3/MeOH in CH2CI2) to yield the title compound as a brown foam.MS (ESI): mass calcd. for C32H32FN5O;?, 537.64; m/z found, 538.5 [M+H]+. 1H NMR (CDCI3): 8.74-8.73 (m, 1 H), 8.62-8.60 (m, 1 H), 7.80-7.76 (m, 2H), 7.60-7.57 (m, 1 H), 7.54-7.50 (m, 1 H), 7.46-7.43 (m, 1 H), 7.33-7.29 (m, 6H), 7.18-7.15 (m, 1 H), 7.09-7.00 (m, 2H), 6.91 (s, 1 H), 6.84-6.77 (m, 1 H), 3.87 (s, 1 H), 3.35-3.32 (m, 2H), 3.05-3.04 (m, 4H), 2.61 -2.58 (m, 4H), 1.16 (t, J = 7.2, 3H)

The synthetic route of 134363-45-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; JANSSEN PHARMACEUTICA, N.V.; WO2009/6185; (2009); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 84199-61-1 , The common heterocyclic compound, 84199-61-1, name is 3-Acetyl-2-bromopyridine, molecular formula is C7H6BrNO, 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 1. 2-Bromo-l-(2-bromopyridin-3-yl)ethanone A solution of l-(2-bromopyridin-3-yl)ethanone (2.10 g, 10.5 mmol) in acetic acid (28.0 mL) was treated with bromine (595 L, 11.5 mmol) and heated at 90 C for 1 h. The reaction mixture was diluted with ethyl acetate and saturated aqueous sodium bicarbonate solution. The aqueous layer was separated and further extracted with ethyl acetate (2 x 80 mL). The combined organic layers were washed with brine, dried over magnesium sulfate, filtered, and concentrated to give the crude product. Purification by flash column chromatography (10% ethyl acetate/hexanes to 30% ethyl acetate/hexanes) gave the desired product (2.15 g, 73%). LCMS calculated for C7H6Br2NO (M+H)+: m/z = 277.9, 279.9, 281.9; found: 277.7, 279.7, 281.8.

The synthetic route of 84199-61-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; INCYTE CORPORATION; COMBS, Andrew P.; SPARKS, Richard B.; MADUSKUIE, Thomas P. Jr.; RODGERS, James D.; WO2014/143768; (2014); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Adding a certain compound to certain chemical reactions, such as: 60010-03-9, 2,6-Dichloro-4-methyl-3-nitropyridine, 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, SDS of cas: 60010-03-9, blongs to pyridine-derivatives compound. SDS of cas: 60010-03-9

A suspension of 2,6-dichloro-4-methyl-3-nitropyridine (300 mg, 1.449 mmol) and sodium bicarbonate (243 mg, 2.90 mmol) in Tetrahydrofuran (THF) (20 mL)) was added (S)- dimethyl 2-aminosuccinate hydrochloride (430 mg, 2.174 mmol) at 0 C under nitrogen. Then the reaction mixture was stirred at 65 C for 24 hr. The reaction was monitored by TLC. The reaction mass filtered and washed with EtOAc (2 x 30 mL). The filtrate was concentrated under reduced pressure to give the crude material. The crude product was added to a neutral alumina column and was eluted with Hex/EtOAc (9: 1). Collected fractions were concentrated under reduced pressure to afford the desired product (250 mg, 0.742 mmol, 51.2 % yield) as yellow gummy liquid, LCMS (m/z) 339.1 (M+H)+.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,60010-03-9, 2,6-Dichloro-4-methyl-3-nitropyridine, and friends who are interested can also refer to it.

Reference:
Patent; GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.2) LIMITED; ELLIS, James Lamond; EVANS, Karen Anderson; FOX, Ryan Michael; MILLER, William Henry; SEEFELD, Mark Andrew; (766 pag.)WO2016/79709; (2016); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem