Day: March 24, 2022

Application of 131747-55-2 ,Some common heterocyclic compound, 131747-55-2, molecular formula is C6H6FNO, 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.

In a 50 ml, three-necked flask fitted with a magnetic stirrer under inert atmosphere,5-chloro-1 H-indole x70 (1.13 g, 7.43 mmol) is dissolved in dry DMF (20 ml). At 00C, NaH(327 mg, 8.18 mmol, 60 % in mineral oil) is added and the mixture is stirred at this temperature for 0.3 h. A solution of 3-(chloromethyl)-2-fluoropyridine x71 (obtained from (2-fluoropyridin-3-yl)methanol and SOCI2 (1.3 g, 8.92 mmol)) in DMF (5 ml) is then added and stirring is continued for 0.5 h at 0 0C. The reaction mixture is poured on ice and the aqueous phase is extracted three times with AcOEt. The combined organic phases are dried over MgSOphi filtered and concentrated. Purification by chromatography on silicagel(Hexane/AcOEt: 9/1 (v/v)) affords 5-chloro-1-[(2-fluoropyridin-3-yl)methyl]-1 H-indole x72 as a solid (1.13 g).Yield: 59 %.1H NMR (250 MHz, DMSO): 5.5 (s, 2H), 6.5 (s,1H), 7.1 (dd, 1H), 7.3 (m, 1 H), 7.4- 7.6 (m, 3H), 7.6 (d, 1H), 8.1 (d, 1H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,131747-55-2, its application will become more common.

Reference:
Patent; UCB S.A.; WO2006/128692; (2006); A2;,
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. 1796-84-5, name is 4-Ethoxy-3-nitropyridine, molecular formula is C7H8N2O3, 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. name: 4-Ethoxy-3-nitropyridine

Example 6 Preparation of 2-amino-4-ethoxy-5-nitropyridine: 2-Amino-4-ethoxy-5-nitropyridine with a melting point of 215 to 217 C. is obtained from 0.34 g of 4-ethoxy-3-nitropyridine, 0.33 g of N,N-tetramethylenethiocarbamoylsulphenamide and 0.6 g of potassium tert.-butylate following the same procedure as in Example 2; the yield is 0.28 g (75%).

With the rapid development of chemical substances, we look forward to future research findings about 1796-84-5.

Reference:
Patent; Bayer Aktiengesellschaft; US5262539; (1993); A;,
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.886365-46-4, name is 5-Chloro-3-methylpyridine-2-carboxylic acid, molecular formula is C7H6ClNO2, molecular weight is 171.58, as common compound, the synthetic route is as follows.HPLC of Formula: C7H6ClNO2

A 100 L r.b. flask was flushed with nitrogen, fitted with thermocouple, overhead stir paddle, and dropping funnel. The flask was charged with a 3M solution of methylmagnesium chloride and stirring begun. The flask was packed in an ice bath. When the temperature reached 5 C., a solution of chloro-ester was added by dropping funnel. The rate of addition was controlled to keep temperature below 30 C., and generally between 20-25 C. After addition was complete, the reaction was aged for 30-45 minutes longer and assayed. The reaction was quenched by addition of ethyl acetate 800 mL followed by methanol 800 mL, again not allowing temperature to rise above 30 C. pH was adjusted with 2N hydrochloric acid solution to pH=4. The acidic reaction solution was extracted with ethyl acetate 9 L. The organic layer was extracted once with 1N hydrochloric acid solution 40 L, and again with 1N hydrochloric acid solution 20 L. The combined aqueous layers were adjusted with 10 N sodium hydroxide to pH=8 (4 L) (Note: an oily layer was noted to separate out on top). The basic aqueous layer was extracted once with ethyl acetate 10 L, dried and concentrated to a solution of 200 mg/mL concentration of product. An aliquot of product solution was concentrated to an oil and purified further by column chromatography on a silica gel 5-10% ethyl acetate in hexanes gradient for characterization purposes. NMR 1H delta: 1.53 (s, 6H), 4.44 (br s, 1H), 7.35 (dd, J=8.4, 0.7 Hz, 1H), 7.66 (dd, J=8.4, 2.4 Hz, 1H), 8.46 (dd, J=2.3, 0.6 Hz, 1H). NMR 13C delta: 30.5, 71.9, 119.5, 130.1, 136.6, 146.4, 164.4.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,886365-46-4, 5-Chloro-3-methylpyridine-2-carboxylic acid, and friends who are interested can also refer to it.

Reference:
Patent; Albaneze-Walker, Jennifer; Ceglia, Scott; Murry, Jerry Anthony; Soheili, Arash; US2004/102472; (2004); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 1044872-40-3, 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. 1044872-40-3, name is Methyl 2-amino-4,6-dichloronicotinate, molecular formula is C7H6Cl2N2O2, 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 13. Preparation of 2-(4-(2-(benzyloxy)ethoxy)-3,5-dimethylphenyl)-5,7-dimethoxypyrido[2,3-d]pyrimidin-4(3H)-one [0196] A mixture of dimethyl acetone-1,3-dicarboxylate (200 g 1.148 mol), cyanamide (48.3 g, 1.148 mol), and Ni(acac)2 (14.75 g, 0.0574 mol) in dioxane (200 mL) was heated to reflux in a 1-L flask with a reflux condenser. The reaction mixture was heated at reflux for 16 hours and then cooled to room temperature. The precipitate was filtered off, and the solid was mixed with methanol (200 mL), stirred for 30 minutes, and filtered again to give methyl 2-amino-4-hydroxy-6-oxo-1,6-dihydropyridine-3-carboxylate (93 g, 44%). [0197] In a 1-L flask with a reflux condenser was added methyl 2-amino-4- hydroxy-6-oxo-1,6-dihydropyridine-3-carboxylate (93.0 g, 0.505 mol) and POCI3 (425 ml_) and the reaction mixture was heated to reflux for 35 minutes. About 300 ml_ POCI3 was evaporated under vacuum. The residue was poured into ice and water (400 ml_), which was further neutralized with KOH to pH approximately 6-7. The precipitate was filtered off and extracted with ethyl acetate (2 x 300 ml_). The organic solution was concentrated and passed through a column, eluting with hexane:ethyl acetate 4:1 , to give methyl 2-amino-4,6-dichloropyridine-3-carboxylate (22.5 g, 20.1%).[0198] In a 500-mL flask with a reflux condenser was added methyl 2- amino-4.6-dichloropyridine-3-carboxylate (22.5 g, 0.101 mol) and 25 wt% sodium methoxide in methanol (88 mL, 0.407 mol), together with methanol (20 ml_). The mixture was heated to reflux for 5 hours, then cooled to room temperature. Acetic acid (15 mL) was added to the mixture and pH was adjusted to approximatley 7. Methanol was removed and the residue was poured into water (100 mL). The precipitated solid was filtered and further rinsed with water (3 * 200 mL) to give methyl 2-amino-4, 6-dimethoxypyridine-3-carboxylate (18.5 g, 86.4%).[0199] In a 500-mL flask with a reflux condenser was added methyl 2-amino-4,6-dimethoxypyridine-3-carboxylate (18.5 g, 0.0872 mol), potassium hydroxide (19.5 g, 0.349 mol) in water (80 mL) and ethanol (100 mL). The mixture was heated to 800C for 16 hours. The solvent was removed and aqueous HCI was used to adjust the pH to 6. The water was removed by freeze drying. The obtained solid was extracted with methanol to yield 2-amino-4,6-dimethoxy-nicotinic acid (17.2 g, 100%).[0200] 2-Amino-4,6-dimethoxy-nicotinic acid (17.2 g, 0.0872 mol) was added to THF (110 mL). 1-[3-(Dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (21.73 g, 0.113 mol), 1-hydroxybenzotriazole hydrate (12.96 g, 0.0959 mol) and 4-methyl morpholine (9.7 g, 0.0959 mol) were then added to the suspension. After stirring for 10 minutes at room temperature, 50% v/v ammonium hydroxide (18.3 g, 0.262 mol) was added. The reaction mixture was kept at room temperature for 16 hours. THF was removed and the residue was poured into cold water (100 mL). The precipitate was filtered off and washed with cold water to yield 2-amino-4,6-dimethoxy-nicotinamide (10.8 g, 62.3%). [0201] To a solution of 4-hydroxy-3,5-dimethylbenzaldehyde (6.84 g, 0.0455 mol) in anhydrous DMF (15 ml_) was added NaH in mineral oil (60%, 2.23 g, 0.0558 mol). (2-Bromo-ethyoxymethyl)-benzene (10.0 g, 0.0465 mol) was added and the reaction was kept at 65C overnight. The reaction mixture was poured into water and extracted with dichloromethane to yield (4-(2-benzyloxy-ethoxy)-3,5-dimethylbenzaldehyde (10.5 g, 81%), which was used for next step reaction without further purification.[0202] To a solution of 2-amino-4,6-dimethoxy-nicotinamide (2.55 g, 12.9 mmol) and 4-(2-benzyloxy-ethoxy)-3,5-dimethylbenzaldehyde (3.68 g, 12.9 mmol) in N,N-dimethyl acetamide (20 ml_), were added NaHSO3 (2.52 g, 14.2 mmol) and p-TSA (1.98 g, 10.4 mmol). The reaction mixture was heated at 1500C for 14 hours. The reaction mixture was cooled to room temperature. The solvent was removed under reduced pressure. The residue was diluted with water and the solid was collected and further washed with methanol. The crude product was purified by column chromatography (silica gel 230-400 mesh; 2% methanol in CH2CI2 as eluent) to give the title compound as an off-white solid (0.88 g, 14.7%). MP 204.5-205.90C.

According to the analysis of related databases, 1044872-40-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; RESVERLOGIX CORP.; HANSEN, Henrik, C.; WAGNER, Gregory, S.; ATTWELL, Sarah, C.; MCLURE, Kevin, G.; KULIKOWSKI, Ewelina, B.; WO2010/123975; (2010); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Adding a certain compound to certain chemical reactions, such as: 184416-84-0, 2,3-Dichloroisonicotinic 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, Recommanded Product: 184416-84-0, blongs to pyridine-derivatives compound. Recommanded Product: 184416-84-0

2,3-Dichloro-isonicotinic acid methyl ester[00197] To a suspension of 2,3-dichloro-isonicotinic acid (7.7 g, 40 mmol) in dichloromethane (45 mL) were added DMF (0.1 mL) and oxalyl chloride (17.5 mL, 200 mmol). The reaction mixture was stirred at room temperature for 18 hours and then concentrated under reduced pressure. The resultant residue was azeotroped with toluene, then cooled to 00C and dissolved in methanol (135 mL). The mixture was allowed to warm to room temperature and then concentrated under reduced pressure to give a residue. The residue was dissolved in ethyl acetate and the resulting solution was washed with a saturated solution of sodium hydrogen carbonate, water and brine, dried (Na2SO4), filtered and concentrated to give the title compound as a colourless oil that crystallised on standing (7.9 g, 96%). 1H NMR (CDCl3, 400MHz) 8.38 (d, J = 5.0 Hz, IH), 7.52 (d, J = 5.0 Hz, IH), 3.99 (s, 3H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound,184416-84-0, 2,3-Dichloroisonicotinic acid, and friends who are interested can also refer to it.

Reference:
Patent; GENENTECH, INC.; WO2009/85980; (2009); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthetic Route of 1083057-12-8, Adding some certain compound to certain chemical reactions, such as: 1083057-12-8, name is tert-Butyl 3-(3-methylpyridin-2-yl)benzoate,molecular formula is C17H19NO2, 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 1083057-12-8.

Preparation of 2-(3-(tert-butoxycarbonyl)phenyl)-3-methylpyridine-1-oxide tert-Butyl-3-(3-methylpyridin-2-yl)benzoate (1.0 eq) was dissolved in EtOAc (6 vol). Water (0.3 vol) was added, followed by urea-hydrogen peroxide (3 eq). Phthalic anhydride (3 eq) was then added portionwise to the mixture as a solid at a rate to maintain the temperature in the reactor below 45 C. After completion of the phthalic anhydride addition, the mixture was heated to 45 C. After stirring for an additional 4 hours, the heat was turned off. 10% w/w aqueous Na2SO3 (1.5 eq) was added via addition funnel. After completion of Na2SO3 addition, the mixture was stirred for an additional 30 min and the layers separated. The organic layer was stirred and 10% wt/wt aqueous. Na2CO3 (2 eq) was added. After stirring for 30 minutes, the layers were allowed to separate. The organic phase was washed 13% w/v aq NaCl. The organic phase was then filtered and concentrated to afford crude 2-(3-(tert-butoxycarbonyl)phenyl)-3-methylpyridine-1-oxide (95%) that was used directly in the next step.

According to the analysis of related databases, 1083057-12-8, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Vertex Pharmaceuticals Incorporated; Verwijs, Marinus Jacobus; (75 pag.)US2016/324788; (2016); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Application of 823221-95-0, 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 823221-95-0, name is 5-Chloro-4-iodo-2-(trifluoromethyl)pyridine. This compound has unique chemical properties. The synthetic route is as follows.

To a solution of 5-Chloro-4-iodo-2-trifluoromethyl-pyridine (7.25 g, 23.6 mmol) in DMSO (70.0 mL) were added diethylmalonate (4.53 g, 28.3 mmol) and cesium carbonate (11.52 g, 35.3 mmol). The reaction mixture was stirred at 100C for 5 h. Reaction completion was confirmed by TLC. Upon cooling, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Crude product was purified by flash column chromatography on silica gel eluting with 10-20% ethyl acetate/hexanes to yield diethyl 2-(5-Chloro-2-trifluoromethyl-pyridin-4-yl)-malonic acid diethyl ester 1. MS ESI/APCI calc’d. for C13H13CIF3NO4[M + H]+339.7, found 340.2.

According to the analysis of related databases, 823221-95-0, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MERCK SHARP & DOHME CORP.; SHAO, Pengcheng Patrick; YE, Feng; VACHAL, Petr; WO2015/94932; (2015); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electric Literature of 902837-42-7, 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.902837-42-7, name is 7-Bromo-1H-pyrrolo[3,2-c]pyridine, molecular formula is C7H5BrN2, molecular weight is 197.032, as common compound, the synthetic route is as follows.

Sodium hydride (0.25 g, 6.2 mmol) is added under ice bath cooling to a mixture of 7-bromo-1H-pyrrolo[3,2-c]pyridine (0.8 g, 4.1 mmol) in DMF (10 ml). The mixture is stirred for 30 minutes before methyl iodide (0.25 ml, 4.1 mmol) is added. The mixture is warmed to RT and stirred for 17 h. The mixture is diluted with DCM and extracted with a saturated aqueous sodium hydrogencarbonate solution. The combined organic layers are dried over MgSO4 and concentrated in vacuo. The product is purified by RP HPLC. Yield: 0.61 g (71%). HPLC-MS: tR=0.88 min (METHOD-1).

Statistics shows that 902837-42-7 is playing an increasingly important role. we look forward to future research findings about 7-Bromo-1H-pyrrolo[3,2-c]pyridine.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; REISER, Ulrich; US2015/57286; (2015); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Adding a certain compound to certain chemical reactions, such as: 75279-39-9, N-(4-Aminopyridin-2-yl)acetamide, 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, Product Details of 75279-39-9, blongs to pyridine-derivatives compound. Product Details of 75279-39-9

Immediately add 45% HBF4 water to solid compound d obtained by rotary evaporation of the above solutionSolution (600mL, 10.8mo1),After stirring, the solid was completely dissolved and ethanol (200 mL) was added.Ice salt bath cooled to below -5C,Isoamyl nitrite (150 mL, 1.12 mol) was added dropwise.Control temperature does not exceed 0 C,And stir the reaction below 0C for 3h.After the reaction was completed, tetrahydrofuran (200 mL) was added.Cool to below 0C,Suction filtrationThe solid was washed twice with tetrahydrofuran (20 mL) and dried in a vacuum desiccator to obtain a solid compound e (213.25 g, 85.3%) with a purity of 96%.The diazonium fluoborate (250g, 1mo1) was put into a dry 1L triple reaction flask.Heat to 120C,Solid decomposition,White smoke emerged from the reaction flask.Continue heating to exhaust white smoke.Solid decomposition is complete.Prepare a 40% NaOH solution (300 mL)The solids on the condenser tube are washed into the reaction flask.Heat reflux,As the product is sublimated,The continuous condensation of solids on the condenserCollect the solids,Repeat the above operation,2-amino-4-fluoropyridine (70 g, 62.5%) was obtained,98% purity.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,75279-39-9, N-(4-Aminopyridin-2-yl)acetamide, and friends who are interested can also refer to it.

Reference:
Patent; Shanghai Lingkai Pharmaceutical Technology Co., Ltd.; Lu Qian; (7 pag.)CN107759515; (2018); A;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Adding a certain compound to certain chemical reactions, such as: 89364-04-5, 3-Bromo-4-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, Computed Properties of C5H3BrN2O2, blongs to pyridine-derivatives compound. Computed Properties of C5H3BrN2O2

Step 5: 5-(2,3-difluoro-4-(4-nitropyridin-3-yl)phenyl)-2-((1-phenyl-2,5,8,11,14-pentaoxahexadecan-16-yl)oxy)pyridine To a solution of 5-(2,3-difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl)-2-((1-phenyl-2,5,8,11,14-pentaoxahexadecan-16-yl) oxy) pyridine (350 mg, 0.544 mmol) in dioxane/H2O (11 mL, 10/1, v/v) was added 3-bromo-4-nitropyridine (121 mg, 0.6 mmol), Na2CO3 (120 mg, 1.1 mmol) and Pd(PPh3)4 (63 mg). The mixture was stirred at 110 C. for 1h under N2. After the reaction, the mixture was extracted with ethyl acetate (20 mL) and washed with brine (30 mL). The organic solution was dried over anhydrous sodium sulfate and concentrated. The crude was purified by column chromatography on silica gel with PE/EA (1:3) to give the desired product (170 mg) as a yellow oil.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,89364-04-5, 3-Bromo-4-nitropyridine, and friends who are interested can also refer to it.

Reference:
Patent; Arvinas, Inc.; Crew, Andrew P.; Berlin, Michael; Flanagan, John J.; Dong, Hanqing; Ishchenko, Alexey; (559 pag.)US2018/125821; (2018); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem