Tag: M.W=100-200

38557-72-1, A common heterocyclic compound, 38557-72-1, name is 2-Chloro-3,5-dimethylpyrazine, molecular formula is C6H7ClN2, 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 2-chloro-3,5-dimethylpyrazine (2.8 g), 1-Boc-piperazine (3.7 g), palladium (II) acetate (225 mg), 2-(dicyclohexylphosphino)-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (953 mg) and sodium tert-butoxide (2.7 g) was added toluene (40 mL), and the mixture was refluxed for 8 hr. After cooling, the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated. The residue was purified by column chromatography (hexane:ethyl acetate) to give 3′,5′-dimethyl-2,3,5,6-tetrahydro[1,2′]bipyrazinyl-4-carboxylic acid tert-butyl ester (5 g). 3′,5′-Dimethyl-2,3,5,6-tetrahydro[1,2′]bipyrazinyl-4-carboxylic acid tert-butyl ester (5 g) was dissolved in chloroform (15 mL), 4N hydrogen chloride/ethyl acetate (15 mL) was added, and the mixture was stirred at room temperature overnight. Ethyl acetate (100 mL) was added, and the mixture was filtered to give the title compound (3.3 g).

The synthetic route of 38557-72-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Mitsubishi Tanabe Pharma Corporation; EP2364975; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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 138588-41-7 as follows. 138588-41-7

7-chloro-N,N,9-trimethyl-2-pyrazin-2-yl-9H-pyrimido[4,5-b]indole-4-carboxamide 0.6 g (26 mmol) of sodium was dissolved under nitrogen in 150 ml of absolute ethanol. Next, 1.2 g (7.6 mmol) of pyrazine-2-carboxamidine hydrochloride was added. After stirring for 1 h 30 min, the residual insoluble part was isolated by filtration and the filtrate was concentrated under reduced pressure. 150 ml of dichloromethane was added and the mixture was filtered. The filtrate was concentrated under reduced pressure. Added to the residue were 100 ml of xylene, then 0.24 g (0.80 mmol) of 2-(2,6-dichloro-1-methyl-1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide, obtained according to step 1.2. from example 1. The mixture was heated under reflux for 18 h. It was then cooled and concentrated under reduced pressure. Dichloromethane, water and a (1M) aqueous solution of sodium hydroxide was added. The organic phase was decanted, washed with water, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column with a mixture of solvents (dichloromethane/ethyl acetate: 80/20 to 0/100, then ethyl acetate/methanol: 100/0 to 95/5). The compound obtained was recrystallized in an ethyl acetate/methanol mixture, it was isolated by filtration, rinsed with diethyl ether and dried under reduced pressure. 0.070 g of 7-chloro-N,N,9-trimethyl-2-pyrazin-2-yl-9H-pyrimido[4,5-b]indole-4-carboxamide was isolated in the form of a white solid. M.P.: 272-273 C. LC/MS: M+H=367 1H NMR (CDCl3, 200 MHz): 9.9 (s, 1H); 8.9 (d, 1H); 8.7 (d, 1H); 8.1 (d, 1H); 7.6 (d, 1H); 7.4 (dd, 1H); 4.1 (s, 3H); 3.4 (s, 3H); 3.1 (s, 3H).

According to the analysis of related databases, 138588-41-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; SANOFI-AVENTIS; US2008/125410; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding some certain compound to certain chemical reactions, such as: 33332-31-9, name is 2-Chloro-5-methoxypyrazine, 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 33332-31-9. 33332-31-9

Preparation of tert-butyl 4-((5-methoxypyrazin-2-yl)oxy)piperidine-l- carboxylate. To a solution of tert-butyl 4-hydroxy-4-methylpiperidine-l-carboxylate (278 mg, 1.38 mmol) in DMF (1.7 mL) was added sodium hydride (60% w/w, 61 mg, 1.52 mmol). The reaction was stirred for 5 min at ambient temperature. Then 2-chloro-5-methoxypyrazine (100 mg, 0.692 mmol) was added and reaction stirred overnight at 95C. The reaction was cooled to ambient temperature and diluted with DCM and washed with saturated NaHC03(aq), water, and brine. The combined organic extracts were dried over anhydrous Na2S04(S), filtered and concentrated in vacuo. The residue was purified by silica chromatography (5-40% EtOAc in hexanes as the gradient eluent) to afford the title compound (assumed quantative yield, 214 mg) in sufficient purity for step 2. MS (apci) m/z = 210.1 (M-Boc).

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 2-Chloro-5-methoxypyrazine.

Reference:
Patent; ANDREWS, Steven W.; ARONOW, Sean; BLAKE, James F.; BRANDHUBER, Barbara J.; COLLIER, James; COOK, Adam; HAAS, Julia; JIANG, Yutong; KOLAKOWSKI, Gabrielle R.; MCFADDIN, Elizabeth A.; MCKENNEY, Megan L.; MCNULTY, Oren T.; METCALF, Andrew T.; MORENO, David A.; RAMANN, Ginelle A.; TANG, Tony P.; REN, Li; WALLS, Shane M.; (946 pag.)WO2018/71454; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 33332-28-4, name is 2-Amino-6-chloropyrazine belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. 33332-28-4

A solution of 82 2-amino-6-chloropyrazine (25 g, 193.1 mmol) in 83 MeOH (500 mL) was treated with 84 NBS (34.3 g, 193.1 mmol), portion-wise, over 1 hour. The resulting mixture was stirred for 16 hours thereafter. TLC analysis at this time shows a small amount of starting material remaining. Another 1.4 g NBS added and reaction heated to 50¡ã C. for 2 hours. The mixture was then cooled to 38¡ã C. and treated with 85 NCS (25.8 g, 193.1 mmol). The reaction mixture was heated to 50¡ã C. for 16 hours thereafter. The mixture was then cooled to room temperature and treated with 39 water (500 mL). The precipitate was collected by filtration and dried in a vacuum desiccator to afford 45.4 g (97percent yield) of 86 2-amino-5-bromo-3,6-dichloropyrazine as a white solid: 13C NMR (75 MHz, CDCl3) ? 149.9 (s), 145.6 (s), 129.6 (s), 121.5 (s). LCMS (15-95percent gradient acetonitrile in 0.1percent TFA over 10 min), single peak retention time=4.51 min on 30 mm column, (M+H)+=244, (M+H+ACN)+=285.

The synthetic route of 33332-28-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MediBeacon Inc.; Debreczeny, Martin P.; Rajagopalan, Raghavan; Dorshow, Richard B.; Neumann, William L.; Rogers, Thomas E.; (54 pag.)US2019/125901; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 6863-74-7, name is 6-Chloropyrazine-2-carbonitrile belongs to Pyrazines compound, it is a common compound, a new synthetic route is introduced below. 6863-74-7

A mixture of tert-butyl ((1R,4R,7R)-2-(1-(azetidin-3-ylmethyl)-2-(1- (cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1H-benzo[d]imidazole- 5-carbonyl)-2-azabicyclo[2.2.1]heptan-7-yl)carbamate (15 mg, 0.024 mmol), 6- chloropyrazine-2-carbonitrile (3.34 mg, 0.024 mmol), cesium carbonate (15.62 mg, 0.048 mmol), BINAP (0.746 mg, 1.199 mmol) and Pd2(dba)3 (1.098 mg, 1.199 mmol) in degassed dioxane (1.0 mL) under nitrogen in a seal vial was stirred at 90C for 18 hour. The mixture was diluted with EtOAc (5 mL) and was washed with a solution of aqueous saturated sodium bicarbonate (5 mL). The organic layer was dried over sodium sulfate and concentrated to give crude tert-butyl ((1R,4R,7R)-2-(1-(azetidin-3-ylmethyl)-2-(1- (cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1H-benzo[d]imidazole- 5-carbonyl)-2-azabicyclo[2.2.1]heptan-7-yl)carbamate (15 mg, 0.024 mmol). Material was used as is in next reaction.

The synthetic route of 6863-74-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; NGU, Khehyong; (435 pag.)WO2020/33514; (2020); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 5521-55-1, name is 5-Methylpyrazine-2-carboxylic acid, molecular formula is C6H6N2O2, 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. 5521-55-1

A solution of compound 20-12 (0.2 g, 0.2 mmol) in isopropanol (2 mL) was cooled to 0 C, and a solution of HC1 in isopropanol (40%, 5 mL) was added. The mixture was stirred until no more gas evolution. The mixture was filtered to afford a white solid; the solid was washed with EtOAc (5 mL). A round-bottom flask was charged with the white solid, compound 22-1 (0.1 g, 0.7 mmol), EDCI (0.2 g, 1.5 mmol) and HOAT (0.15 g, 1.1 mmol), and then DCM (10 mL) was added under N2. The mixture was cooled to 0 C, and DIPEA (0.5 mL, 3 mmol) was added slowly. The mixture was stirred at 30 C for 6 hours. After the reaction was complete, the mixture was quenched with water (10 mL). The resulting mixture was extracted with DCM (10 mL) twice. The combined organic layers were washed with saturated aqueous NaC1 (10 mL), dried over anhydrous Na2SO4, and then concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with PE : EtOAc (V:V) = 2:1 to give compound 20-2 (0.163 g, 70%) as a white solid.MS (ESI, pos.ion) m/z: 900.4[M+1] and ?HNMR (600 MHz, CDC13): (510.25 (s, 1H), 9.07 (s, 1H), 8.43 (s, 1H), 8.17 (d, J= 6.8 Hz,1H), 7.86-7.78 (m, 2H), 7.48 (s, 1H), 7.05 (s, 1H), 6.95 (d, J 9.1 Hz, 1H), 5.74 (dd, J 18.0,8.6 Hz, 1H), 5.51 (s, 1H), 5.02 (t, J= 9.5 Hz, 1H), 4.72-4.65 (m, 2H), 4.51 (d, J= 11.4 Hz, 1H),4.14-4.11 (m, 1H), 3.78 (s, 3H), 3.26-3.19 (m, 2H), 2.74-2.69 (m, 1H), 2.67-2.55 (m, 9H),2.29 (dd, J= 17.3, 8.6 Hz, 1H), 2.07 -2.00 (m, 2H), 1.95 – 1.89 (m, 2H), 1.78 (t, J= 10.0 Hz,1H), 1.64 (dd, J= 9.2, 5.9 Hz, 1H), 1.50 (s, 3H), 1.41 (d, J= 6.9 Hz, 7H), 1.27 (d, J= 3.5 Hz,2H), 1.20 (s, 3H), 0.92- 0.75 (m, 3H) ppm.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5521-55-1, its application will become more common.

Reference:
Patent; SUNSHINE LAKE PHARMA CO., LTD.; ZHANG, Yingjun; LUO, Huichao; REN, Qingyun; XIONG, Zhimin; LIU, Yang; LEI, Yibo; XIONG, Jinfeng; ZHANG, Jiancun; (123 pag.)WO2016/127859; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem