Month: April 2022

Reference of 75893-75-3, 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. 75893-75-3, name is 6-Cyclopropylnicotinic acid. A new synthetic method of this compound is introduced below.

Example 56 6-Cyclopropyl-N-([2-fluoro-4-[2-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]phenyl]methyl)pyridine-3-carboxamide (56) In a 10-mL round bottom flask purged and maintained with an inert atmosphere of nitrogen, [2-fluoro-4-[2-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]phenyl]methanamine (100 mg, 0.31 mmol, 1.00 equiv) and 6-cyclopropylpyridine-3-carboxylic acid (60.7 mg, 0.37 mmol, 1.20 equiv) were dissolved in N,N-dimethylformamide (2 mL), to which were added HATU (176.9 mg, 0.47 mmol, 1.50 equiv) and DIEA (120.3 mg, 0.93 mmol, 3.00 equiv) in sequence at room temperature. The resulting solution was stirred for 16 h at room temperature. When the reaction was done, it was quenched by the addition of 5 mL water and the mixture was extracted with dichloromethane (3*10 mL). The organic layers were combined, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by prep-HPLC using the following conditions: column, X Bridge C18, 19*150 mm, 5 um; mobile phase, acetonitrile in water (with 0.05% TFA), 30% to 70% gradient in 10 min; detector, UV, 254 nm. 6-cyclopropyl-N-([2-fluoro-4-[2-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-7-yl]phenyl]methyl)pyridine-3-carboxamide (20 mg, 13%) was obtained as white solid. HPLC: 97.7% purity. MS: m/z=468.1 [M+H]+. 1H NMR (400 MHz, DMSO-d6): 6 13.39 (br s, 1H), 9.20-9.17 (m, 1H), 8.91 (d, J=2.0 Hz, 1H), 8.44 (s, 1H), 8.29-8.20 (m, 2H), 8.14-8.11 (m, 3H), 7.56-7.52 (m, 2H), 7.42 (d, J=8.0 Hz, 1H), 4.60 (s, 2H), 3.94 (s, 3H), 2.33-2.15 (m, 1H), 1.05-1.01 (m, 4H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound,75893-75-3, 6-Cyclopropylnicotinic acid, and friends who are interested can also refer to it.

Reference:
Patent; Merck Patent GmbH; GAILLARD, Pascale; SEENISAMY, Jeyaprakashnarayanan; LIU-BUJALSKI, Lesley; CALDWELL, Richard D.; POTNICK, Justin; QIU, Hui; NEAGU, Constantin; JONES, Reinaldo; WON, Annie Cho; GOUTOPOULOS, Andreas; SHERER, Brian A.; JOHNSON, Theresa L.; GARDBERG, Anna; (234 pag.)US2016/96834; (2016); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 201937-23-7 ,Some common heterocyclic compound, 201937-23-7, molecular formula is C6H7Cl2N3, 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.

Compound 88 (1.08 g, 3.14 mmol), 6-chloropyridine-3-carboxirnidamide hydrochloride (900 mg, 4.69 mmol) and K2CO3 (1.30 g, 9.42 mmol) in EtOH (15 mL) were heated in a Biotage microwave synthesizer at 120 C for 3 h. After the reaction was cooled to room temperature, EtOAc was added. The mixture was washed with water. The organic extract was dried with Na2S04and concentrated. The crude product was dissolved in CH2CI2 (31 mL) and treated with DDQ (713 mg, 3.14 mmol). After the reaction was stirred at room temperature for 1 h, aq. sat. NaHCCb was added. The mixture was stirred at room temperature for 10 min; filtered through a pad of Celite; and eluted with CH2CI2. The organic phase of the filtrate was separated. The aqueous phase was extracted with CH2CI2. The combined organic extract was dried with Na2S04 and filtered and concentrated. The residue was purified by flash chromatography (silica gel, eluting with 0% to 5% EtOAc in CH2CI2) to give compound 363 (902 g, 60% yield) as a white foamy solid, m/z = 480 (M+l).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,201937-23-7, its application will become more common.

Reference:
Patent; REATA PHARMACEUTICALS, INC.; JIANG, Xin; BENDER, Christopher, F.; VISNICK, Melean; HOTEMA, Martha, R.; SHELDON, Zachary, S.; LEE, Chitase; CAPRATHE, Bradley, William; BOLTON, Gary; KORNBERG, Brian; (497 pag.)WO2018/111315; (2018); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 17570-98-8, Adding some certain compound to certain chemical reactions, such as: 17570-98-8, name is 2-(Bromoacetyl)pyridine hydrobromide,molecular formula is C7H7Br2NO, 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 17570-98-8.

EXAMPLE 17 2-Pyridin-4-yl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one (alternative method) Bromoacetylpyridine hydrobromide (3.3 g, 11.78 mmol), piperidindione (2 g, 17.68 mmol) and ammonium acetate (3.63 g, 47.1 mmol) were dissolved in anhydrous ethanol (54 mL) and stirred at RT overnight. Ethyl acetate (200 mL) was added (precipitate formed) and the mixture was stirred at RT for 30′. The solid was filtered off and discarded, while the solution was concentrated under reduced pressure. The residue (orange-red solid, 4.8 g) was purified by flash chromatography (eluant DCM/MeOH 6:1). To the obtained pink solid (1.34 g, 6.28 mmol), dissolved in MeOH (140 mL), 4N HCl in dioxane (3.14 mL, 12.56 mmol) was added. The mixture (precipitate) was stirred for 30′, then concentrated under reduced pressure to half of the volume, stirred 30′ and filtered to yield the first crop (1.3 g). The mother liquor was concentrated to 20 mL and the second crop filtered out (0.12 g). The two crops were joined and washed twice with 95% EtOH: first with 35 mL and 2 hours stirring, the second with 25 mL of ethanol. The collected solid was dried to yield 1.21 g of desired compound (41.1% yield, purity>90%). By working in an analogous way and starting from the corresponding bromoketoheteroaryl the following compounds were also obtained:

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. 17570-98-8, 2-(Bromoacetyl)pyridine hydrobromide, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Pharmacia Italia S.p.A.; US2007/142414; (2007); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

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. 69422-72-6, name is 2,4,6-Trichloronicotinic acid, molecular formula is C6H2Cl3NO2, 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. Application In Synthesis of 2,4,6-Trichloronicotinic acid

A solution of the product of EXAMPLE 14C (1.5 g, 6.7 mmol) in dichlorom ethane (50 mL) was treated at room temperature with 2 drops of N,N-dimeth lformamide. O alyl chloride (1.27 g, 10 mmol) was added dropwise over 15 minutes and stirring was continued for 2 hours. The solution was concentrated and dried under vacuum to give the crude acid chloride. Ammonium (gas) was passed through a solution of the acid chloride in tetrahydrofuran (20 mL) and the mixture stirred at room temperature for 0.5 hours. The mixture was concentrated under vacuum and the residue purified by flash chromatography on silica gel (200-300 mesh) eluting with 100/1 dichloromethane/methanol to give the title compound. MS: 225 (M+H+).

With the rapid development of chemical substances, we look forward to future research findings about 69422-72-6.

Reference:
Patent; ABBOTT LABORATORIES; VASUDEVAN, Anil; PENNING, Thomas, Dale; CHEN, Huanming; LIANG, Bo; WANG, Shaohui; ZHAO, Zhongqiang; CHAI, Dikun; YANG, Leifu; GAO, Yingxiang; WO2012/97479; (2012); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 630395-95-8, name is 1H-Pyrrolo[3,2-c]pyridine-2-carbaldehyde. This compound has unique chemical properties. The synthetic route is as follows. Recommanded Product: 1H-Pyrrolo[3,2-c]pyridine-2-carbaldehyde

To a solution of lH-pyrrolo[3,2-c]pyridine-2-carbaldehyde (3.24 g, 22.19 mmol) in MeOH at 0C under argon is added sodium cyanide (5.44 g, 111 mmol) and manganese dioxide (9.65 g, 111 mmol). The reaction mixture is stirred for 5h after which time it is filtered through Celite and diluted with EtOAc (500mL). The organic layer is washed with water (2x), brine, dried over sodium carbonate, filtered and concentrated to yield 3.27 g ( 84%) of desired product. 1H NMR (DMSO-dtf, 300 MHz) delta 12.3 (bs, 1H), 9.0 (s, 1H), 8.3 (d, 1H), 7.4 (d, 1H), 7.3 (s, 1H), 4.0 (s, 3H). LCMS m/z 177 (M+H).

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, 630395-95-8, 1H-Pyrrolo[3,2-c]pyridine-2-carbaldehyde.

Reference:
Patent; SANOFI; CHOI-SLEDESKI, Yong Mi; NIEDUZAK, Thaddeus R.; POLI, Gregory B.; SHUM, Patrick Wai-Kwok; STOKLOSA, Gregory T.; ZHAO, Zhicheng; WO2011/78984; (2011); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Reference of 1060810-03-8, 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. 1060810-03-8, name is 5-Chloro-2-methylisonicotinic acid. A new synthetic method of this compound is introduced below.

To a CH2Cl2 solution of acid 6-4 (0.8 g) was added EDC (1.3 eq) and aniline (2 eq) at room temperature. After 10 minutes, the reaction was diluted with CH2Cl2 and washed with dilute HCl. The organic layer was dried and concentrated to yield amide 6-5 (0.9 g, 80%) .

At the same time, in my other blogs, there are other synthetic methods of this type of compound,1060810-03-8, 5-Chloro-2-methylisonicotinic acid, and friends who are interested can also refer to it.

Reference:
Patent; BIOTA SCIENTIFIC MANAGEMENT PTY LTD; WO2008/141385; (2008); 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.88912-24-7, name is 5,6-Dichloropicolinic acid, molecular formula is C6H3Cl2NO2, molecular weight is 192, as common compound, the synthetic route is as follows.COA of Formula: C6H3Cl2NO2

Sodium hydride (CAN 7646-69-7, 60% w/w, 1.05 g, 26 mmol) was added to cyclopropylmethanol (CAN 2516-33-8, 7.5 g) at 0 C. and the mixture was stirred for 1 h. 5,6-Dichloro-pyridine-2-carboxylic acid (1 g, 5 mmol) was added and the mixture was heated to 95 C. for 3 h. The solvent was removed under reduced pressure. The residue was diluted with water (10 mL) and adjusted to pH=3.0 by hydrochloric acid (3 N). The solution was extracted with ethyl acetate (3×15 mL). The combined organic layers were washed with water (3×30 mL) and brine (2×40 mL) and evaporated to dryness to give the crude product (0.35 g, 25%), which was used in the next step without further purification, MS (EI): m/e=228.1 [M+H]+.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,88912-24-7, 5,6-Dichloropicolinic acid, and friends who are interested can also refer to it.

Reference:
Patent; Bissantz, Caterina; Grether, Uwe; Hebeisen, Paul; Kimbara, Atsushi; Liu, Qingping; Nettekoven, Matthias; Prunotto, Marco; Roever, Stephan; Rogers-Evans, Mark; Schulz-Gasch, Tanja; Ullmer, Christoph; Wang, Zhiwei; Yang, Wulun; US2012/316147; (2012); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 884495-01-6, 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.884495-01-6, name is 4-Bromo-5-fluoro-2-hydroxypyridine, molecular formula is C5H3BrFNO, molecular weight is 191.99, as common compound, the synthetic route is as follows.

2.08 mL (26.0 mmol) Ethyl iodide and 1 .08 g (3.91 mmol) Ag2CO3 are added to a mixture of 500mg (2.160 mmol) 4-bromo-5-fluoro-pyridin-2-ol in 10 mL DCM. The mixture is stirred at r.t. over night. Then the reaction mixture is quenched by the addition of water and DCM. After filtration the org. layer is separated, dried with Na2SO4 and the solvent is removed in vacuo.C7H7BrFNO (M = 220.0 g/mol)ESI-MS: 220 [M+H]+ Rt (HPLC) : 1 .27 mm (method X)

The chemical industry reduces the impact on the environment during synthesis 884495-01-6, I believe this compound will play a more active role in future production and life.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; FLECK, Martin; ROTH, Gerald Juergen; NOSSE, Bernd; HEINE, Niklas; WO2013/92616; (2013); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 700811-29-6 ,Some common heterocyclic compound, 700811-29-6, molecular formula is C5H6ClN3, 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 solution of 4-amino-2-chloropyridine (1.0 g, 7.78 mmol) in 20% sulfuric acid (20 mL) was cooled to 0 C and treated with a solution of sodium nitrite (564 mg, 8.17 mmol) in water (3 mL) at a rate such that the reaction temperature did not exceed 10 C. After 15 minutes, the solution was added to a 0C suspension of tin (li) chloride in 20% sulfuric acid (20 mL). The frothy suspension was stirred for 15 minutes at 0 C and then warmed to room temperature over 15 minutes. The mixture was poured into 100 mL of ice water and made basic with concentrated ammonium hydroxide. The product was extracted with diethyl ether and ethyl acetate repeatedly. The organic layers were dried (sodium sulfate) and concentrated to give crude 2-chloro-4-hydrazinopyridine as a yellow solid (830 mg, 5.78 mmol). The solid was dissolved in tetrahydrofuran (5 mL) and diluted with diethyl ether (15 mL). The solution was treated with 1 N HCI in diethyl ether (5.8 mL, 5.8 mmol). The white precipitate was filtered and washed with ether to give 2-chloro-4-hydrazinopyridine hydrochloride as a white solid (995 mg, 5.53 mmol, 71 % yield). LC-MS (ES+) MH+ = 144.’H NMR (300 MHz, DMSO-d6) b 10.0-9. 40 (br s, 4H), 8.07 (d, J = 6. 1, 1 H), 6.95 (d, J = 1.9, 1 H), 6.86 (dd, J = 5.8, 2.0, 1H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,700811-29-6, its application will become more common.

Reference:
Patent; PHARMACIA CORPORATION; WO2004/58176; (2004); A2;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Adding a certain compound to certain chemical reactions, such as: 75711-01-2, 6-Chloro-5-methoxypyridin-3-amine, 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, 75711-01-2, blongs to pyridine-derivatives compound. Safety of 6-Chloro-5-methoxypyridin-3-amine

To an ice-cooled suspension of 6-chloro-5-(methyloxy)-3-pyridinamine D46 (2.14 g, 13.50 mmol) in HCl 4 M in water (10.12 ml, 40.50 mmol), a solution of sodium nitrite (1.02 g, 14.84 mmol) in water (7 ml) was added dropwise over a 5 min period and the resulting mixture was vigorously stirred at 5 C. for 30 min. To the mixture at 5 C. was added a solution of NaBF4 (2.67 g, 24.29 mmol) in water (17 ml). The thick suspension was collected by filtration, washed with cold water and a little amount of cold EtOH and dried under reduced pressure at 55 C. for 8 h. The resulting black solid was taken-up in xylenes (25 ml) and allowed to reflux for 1 h. The solvent was evaporated under reduced pressure, the residue dissolved in EtOAc and washed with a saturated NaHCO3 aqueous solution. The organic phase was separated, dried (Na2SO4), filtered and the solvent removed under vacuum. The resulting black oil was purified by flash chromatography on silica gel (Biotage SP4 25M, Cy/EtOAc 95/5) to afford the title compound D47 (0.11 g, 0.69 mmol, 5% yield) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) delta (ppm): 8.03 (d, 1H), 7.70 (dd, 1H), 3.92 (s, 3H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,75711-01-2, its application will become more common.

Reference:
Patent; ALVARO, GIUSEPPE; AMANTINI, DAVID; BELVEDERE, SANDRO; US2009/22670; (2009); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem