Category: pyridine-derivatives

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.10167-97-2, name is 2-Amino-5-methoxypyridine, molecular formula is C6H8N2O, molecular weight is 124.1405, as common compound, the synthetic route is as follows.Formula: C6H8N2O

(a) 2-Amino-5-methoxypyridine (14.8 g, prepared by the method of J.G. Lombardino, J. Med. Chem., 1981, 24, 39) was dissolved in 60% hydrobromic acid (150 ml) and to the cooled (-10) stirred solution bromine (47.47 g) was added dropwise. To the resulting yellow suspension was added, dropwise, sodium nitrite (20.53 g) in water (40 ml), keeping the temperature below -5. The mixture was stirred to room temperature, and after 0.5 hour cooled to 0, and a solution of sodium hydroxide (120 g) in water (100 ml) was slowly added. The mixture was thoroughly extracted with ether, the combined ether extracts dried with anhydrous sodium sulphate, and evaporated. The residue was chromatographed on silica gel (150 g). Elution with dichloromethane gave a yellow oil (14.1 g, 63%) which was combined with a smaller batch (3.4 g) and distilled under reduced pressure to give 2-bromo-5-methoxypyridine (16.4 g). b.p. 76-78/0.6 torr.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,10167-97-2, 2-Amino-5-methoxypyridine, and friends who are interested can also refer to it.

Reference:
Patent; Smith Kline & French Laboratories Ltd.; US4766121; (1988); A;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Adding a certain compound to certain chemical reactions, such as: 884494-82-0, 5-Fluoro-2-methoxynicotinic 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, 884494-82-0, blongs to pyridine-derivatives compound. Formula: C7H6FNO3

[0429] A solution of 2-(4-(4-fluorobenzd)piperazin-l-yl)-6-methylpyridin-3-arnine (72 mg, 0.240 rnmol), 5-fluoro-2-methoxynicotinic acid (123 mg, 0.719 mmol), HATU (273 mg, 0.719 mmol) and DIPEA (167 muEpsilon, 0,959 mmol) in DMF (1199 muEpsilon) was stirred on a hot plate at 80C overnight. The reaction mixture was filtered through a Millipore filter, diluted with DMF and MeOH and purified by HPLC (Sliimadzu) eluting with a gradient of ACN in water (basic mode) to give the title compound as a pale brown solid (64.6 mg, 59.4%). NMR (400 MHz, CDCb) delta ppm 2,46 (s, 3 H), 2.64 (br s, 4 H), 3.14 (br s, 4 H), 3,60 (br s, 2 H), 4.16 (s, 3 H), 6.91 (d, J=8,08 Hz, 1 H), 7.03 (t, /=8.59 Hz, 2 H), 7.32 (br s, 2 H), 8.17 (d, J=3.28 Hz, 1 H), 8.36 (dd, (1382) -8.08 Hz, 1 H), 10.31 (br s, 1 H); ESI-MS m/z j M H | ‘ 454.3. (1383) (1384) [0430] The preparation of Example 100 yielded the title compound as a des-methyl side product which was recovered as an orange solid (12.4 mg, 11.8%). NMR (400 MHz, CDCb) delta ppm 2.40 – 2.47 (m, 3 H), 2.82 (br s, 4 H), 3,27 (br s, 6 H), 6,89 id. ./ 8.08 Hz, 1 H), 7,03 (t, ./ 7.96 Hz, 2 H), 7.42 (br s, 2 H), 7,55 (br s, 1 H), 8,53 – 8.64 (m, 2 H), 11.69 – 11,88 (m, 1 H); ESI-MS m/z [M+H]” 440.3.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,884494-82-0, its application will become more common.

Reference:
Patent; TAKEDA PHARMACEUTICAL COMPANY LIMITED; GREEN, Jason; HOPKINS, Maria; JONES, Benjamin; KIRYANOV, Andre A.; KUEHLER, Jon; MONENSCHEIN, Holger; MURPHY, Sean; NIXEY, Thomas; SUN, Huikai; (300 pag.)WO2018/183145; (2018); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Adding a certain compound to certain chemical reactions, such as: 863704-60-3, 6-(4-Fluorophenyl)picolinic 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, Quality Control of 6-(4-Fluorophenyl)picolinic acid, blongs to pyridine-derivatives compound. Quality Control of 6-(4-Fluorophenyl)picolinic acid

A mixture of picolinic acid derivative (1.0 g, 4.6 mmol), Na2HPO4 (1.2 g) and m-CPBA (1.1 g, 70% from Aldrich) in CH2ClCH2Cl (30 mL) was stirred at rt for 2 h. Additional Na2HPO4 (0.8 g) and m-CPBA (1.0 g) was added to the reaction mixture and it was stirred for 3 h at rt. Another Na2HPO4 (0.5 g) and m-CPBA (0.5 g) was added to the reaction mixture and it was stirred at rt overnight. CHCl3 (160 mL) and 2 N aq. HCl solution (50 mL) were added to the reation mixture and the organic layer was separated, dried over MgSO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with EtOAc/MeOH/HOAc//700:240:60 to obtain the desired product which was contaminated with m-CPBA. This impure material was purified by preparative HPLC to obtain the desired product (175 mg, 16%) as a white solid. 1H NMR (DMF-d7) 8.45 (dd, 1H, J=8.3, 2.2 Hz), 8.15 (d, 1H, J=2.2 Hz), 8.13-8.00 (m, 4H), 7.45 (t, 2H, J=8.7 Hz).

At the same time, in my other blogs, there are other synthetic methods of this type of compound,863704-60-3, 6-(4-Fluorophenyl)picolinic acid, and friends who are interested can also refer to it.

Reference:
Patent; Borzilleri, Robert M.; Cornelius, Lyndon A.M.; Schmidt, Robert J.; Schroeder, Gretchen M.; Kim, Kyoung S.; US2005/245530; (2005); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 1086838-13-2 , The common heterocyclic compound, 1086838-13-2, name is 5-Chloro-3-nitropicolinaldehyde, molecular formula is C6H3ClN2O3, 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.

a. To a solution of 5-chloro-3-nitropyridine-2-carboxaldehyde (1 g), described in Example 146, in 1,2-dichloroethane (20 mL) was added 4 A molecular sieves powder and 2-(tert-butyldimethylsilanyloxy)propylamine (1.22 g) described in Example 105 part a. After stirring overnight at room temperature, sodium cyanoborohydride (0.4 g) and acetic acid (0.33 mL) were added at 0 C. After stirring for one hour at 0 C., the reaction mixture was heated to 65 C. overnight. The reaction mixture was filtered through a plug of Celite and concentrated under reduced pressure to yield a residue that was purified by chromatography (SiO2, heptane/EA) to afford 2-[2-(tert-butyldimethylsilanyloxy)propyl]-6-chloro-2H-pyrazolo[4,3-b]pyridine (0.6 g, 37%). MS (ES): M/Z [M+H]=326. 1H NMR: (400 MHz, CHLOROFORM-d): -0.37 (s, 3H), -0.09 (s, 3H), 0.79 (s, 9H), 1.24 (d, J=6.1Hz, 3H), 4.21-4.31 (m, 1H), 4.33-4.38 (m, 1H), 4.40-4.47 (m, 1H), 8.00 (dd, J=2.1, 0.9 Hz, 1H), 8.22 (d, J=0.7Hz, 1H) and 8.48 (d, J=2.1Hz, 1H).

The synthetic route of 1086838-13-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AVENTIS AGRICULTURE; MERIAL LIMITED; Soll, Mark David; Le Hir de Fallois, Loic Patrick; Huber, Scot Kevin; Lee, Hyoung Ik; Wilkinson, Douglas Edward; Jacobs, Robert Toms; US2014/80862; (2014); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 65515-26-6, 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. 65515-26-6, name is Methyl 2,6-dimethoxynicotinate. A new synthetic method of this compound is introduced below.

Under nitrogen atomosphere, 15 % hexane solution of triethyl aluminium was dropped at 0C to 26 m solution of toluene with 0.6 ml of N,N’-dimethyl-ethan-1,2-diamine, and the mixture was stirred at room temperature for 1 hour. Then, 5 ml solution of toluene with 1 g of 2,6-dimethoxy-nicotinic acid methylester was dropped at room temperature, and the mixture was stirred at 130C for 1 hour. The reaction solution was cooled down under ice temperature, 1M of hydrochloric acid was added, and extracted with ethyl acetate. Ethyl acetate layer was washed with saturated saline solution, dried with anhydrous sodium sulfate. The solvents were distilled outunder reduced pressure to obtain 156 mg of the above compound. ESI-MS Found:m/z 196.1 [M+H]+

At the same time, in my other blogs, there are other synthetic methods of this type of compound,65515-26-6, Methyl 2,6-dimethoxynicotinate, and friends who are interested can also refer to it.

Reference:
Patent; BANYU PHARMACEUTICAL CO., LTD.; EP1726585; (2006); 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.51173-05-8, name is 5-Fluoro-2-hydroxypyridine, molecular formula is C5H4FNO, molecular weight is 113.09, as common compound, the synthetic route is as follows.COA of Formula: C5H4FNO

Intermediate 4,4-fluoro-7-bromo-6-azaindole, was prepared according to the following scheme: [CHEMMOL-00081] [0364] A) fuming HNO3, H2SO4; [0365] B) POBr3/DMF, 110 C.; [0366] C) vinylmagnesium bromide, THF, -78 C. -20 C. [0367] Intermediate 4 was isolated as a brownish solid. MS m/z: (M+H)+ calcd for C7H5BrFN2: 214.96; found 214.97. HPLC retention time: 1.28 minutes (column G).

At the same time, in my other blogs, there are other synthetic methods of this type of compound,51173-05-8, 5-Fluoro-2-hydroxypyridine, and friends who are interested can also refer to it.

Reference:
Patent; Kadow, John F.; Regueiro-Ren, Alicia; Xue, Qiufen May; US2004/6090; (2004); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 610278-88-1, 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.610278-88-1, name is 3,5-Dichloro-2-nitropyridine, molecular formula is C5H2Cl2N2O2, molecular weight is 192.9876, as common compound, the synthetic route is as follows.

b) 5′-Chloro-4-methyl-2′-nitro-3,4,5,6-tetrahydro-2H-[l,3′]bipyridinyl; A mixture of 3,5-dichloro-2-nitropyridine (193 mg, 1.00 mmol), A- methylpiperidine (118 muL, 1.00 mmol) and K2CO3 (138 mg, 1.00 mmol) in toluene (10 mL) was heated at 50 C for 3h. Toluene was removed in vacuo and the residue obtained was purified on silica (2 % EtOAc/ hexane) to obtain the title compound (153 mg, 60%). 1H-NMR (CDCl3; 400 MHz): delta 7.95 (s, IH, J=2.5 Hz), 7.58 (s, IH, J=2.5 Hz), 3.30 (m, 2H), 2.95 (m, 2H), 1.87 (m, 2H), 1.65 (m, IH), 1.35 (m, 2H), 1.0 (d, 3H, J=6.3 Hz).

Statistics shows that 610278-88-1 is playing an increasingly important role. we look forward to future research findings about 3,5-Dichloro-2-nitropyridine.

Reference:
Patent; JANSSEN PHARMACEUTICA, N.V.; WO2006/47504; (2006); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 78760-60-8 ,Some common heterocyclic compound, 78760-60-8, molecular formula is C13H10N2O, 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 D: at -5 ~ 0 , a 2M ethylmagnesium bromide in THF (26.5mL, 53mmol) was added dropwise to compound 25 (8.6g, 40.9mmol) in THF (30 mL) solution. After the addition was completed, the resulting mixture was further stirred at this temperature for 1 hour. Slowly add water (90mL),Adjust the pH to 3~4 with 2M hydrochloric acid.Extracted with ethyl acetate (100 mL × 3),The combined organic phases were washed with water (50 mL) and brine brineThe solvent was evaporated under reduced pressure to give 1-(5-benzyloxypyridin-2-yl)propan-1-one (26) (9.74 g). The yield was 98.7%.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,78760-60-8, its application will become more common.

Reference:
Patent; Jiangsu Xin Element Pharmaceutical Technology Co., Ltd.; Shi Dongfang; Fu Changjin; Cheng Xi; Gong Weiwei; Gu Jie; Li Pengfei; Zhang Min; Yang Yan; Jin Wenqing; (51 pag.)CN110183431; (2019); A;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 67938-76-5, 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. 67938-76-5, name is (5-Chloropyridin-2-yl)methanamine. A new synthetic method of this compound is introduced below.

General procedure: Example 6A (2 g, 6.35 mmol) and (4-fluorophenyl)methanamine (0.794 g, 6.35 mmol) in acetonitrile (10 ml) were stirred at 120 °C overnight. The reaction mixture was cooled, concentrated, taken into ethyl acetate and washed with saturated aqueous NaHC03 and brine. The combined aqueous layers were extracted twice with ethyl acetate. The combined organic extracts were dried (MgS04) and filtered. The filtrate was concentrated until solid material precipitated. The mixture was filtered to provide the title compound.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,67938-76-5, (5-Chloropyridin-2-yl)methanamine, and friends who are interested can also refer to it.

Reference:
Patent; ABBVIE INC.; SWEIS, Ramzi F.; CURTIN, Michael L.; PLIUSHCHEV, Marina A.; HANSEN, Todd M.; LONGENECKER, Kenton; WO2013/170118; (2013); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 670253-37-9, 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 670253-37-9, name is 4-Chloro-5-iodopyridin-2-amine. This compound has unique chemical properties. The synthetic route is as follows.

To a solution of 4-chloro-5-iodo-pyridin-2-ylamine (64.2 g, 0.25 mol) in methanol (1.1 L) and TFA (93.7 mL, 1.26 mol) was added tert-butyl nitrite (150 mL, 1.26 mol) so as to maintain temperature less than 3 C. The resultant mixture was stirred at RT for 1 h then allowed to warm to RT and stirred for 16 h. The reaction was quenched by the careful addition of water then concentrated in vacuo to one-fourth of the volume. The resultant residue was treated with water (1 L) and the precipitate formed collected by filtration and dried in vacuo at 35 C. to give the title compound (62.3 g, 92%). Contains 16% impurity. 1H NMR 400 MHz (DMSO-d6) delta: 8.56 (1H, s), 7.20 (1H, s), 3.86 (3H, s).

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 670253-37-9, 4-Chloro-5-iodopyridin-2-amine.

Reference:
Patent; Genentech, Inc.; US2012/245144; (2012); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem