Tag: M.W=100-200

Some common heterocyclic compound, 1174321-06-2, name is 5-(Difluoromethyl)pyrazine-2-carboxylic acid, molecular formula is C6H4F2N2O2, 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. category: Pyrazines

5-(Difluoromethyl)pyrazine-2-carboxylic acid 42 (0.68 wt, 1.1 eq) was charged into a reactor and if needed, dried by azeotropic distillation with toluene. DMI (2.0V) was added and the mixture was cooled down to 0-5 C. Thionyl chloride (0.337 V, 1.30 eq) was added while keeping the internal T below 10 C. The resulting solution was stirred at 4-10 C until the conversion was >95.0 % by HPLC. The mixture was cooled down to 0 C and a solution of 39 (1.0 Wt, 1.0 eq) in DMI (2.5V) was charged while keeping the internal temperature below 5 C. The vessel was rinsed with DMI (0.50V) and the reaction mixture was stirred until the conversion is >99%. Water (12V) was charged and the resulting mixture is stirred at 15-20 C for 0.5h. EtOAc (15V) and then 50% aq. NaOH (1.5 Wt, 5.3 eq) were added while keeping T below 30 C. pH was monitored to make sure that it is above 10. The aqueous phase was separated and extracted with EtOAc (5.0V). Theorganic layers were combined and washed with brine (5.0V) and water twice (5.0V each). The mixture was filtered through a Celite pad (0.50 Wt) rinsing with EtOAc (3.0V). The filtrate was concentrated under reduced pressure at 40-50 C. 1-Propanol (15V) was charged and the mixture was warmed up to 90-100 C while stirring until a clear solution was obtained. The mixture was cooled down to 0-5 C over 2h and stired over lh. The mixture was filtered, rinsing with cold 1-propanol twice (2.5V each). Drying in an oven vacuum at 45 C overnight provided the title compound 43 as an off-white solid in 81% isolated yield.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 1174321-06-2, its application will become more common.

Reference:
Patent; ???????????????????????????; ? Buranko; Kimu ?; Chan ?; ?; Yoshizawa Kazuhiro; (94 pag.)JP2016/121177; (2016); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 36070-80-1, name is 5-Chloropyrazine-2-carboxylic acid, belongs to pyrazines compound, 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 36070-80-1, Product Details of 36070-80-1

The 5-cyclopropylmethoxy-pyrazine-2-carboxylic acid was obtained as follows:; A solution of 5-chloro-pyrazine-2-carboxylic acid (1.5 g, 9.46 mmol) in dry dimethylsulphoxide (5 ml) was treated with cyclopropyl-methanol (1.15 ml, 14.1 mmol) and powdered potassium hydroxide (2.12 g, 37.8 mmol). The mixture was irradiated in a microwave vessel at 80 C. for 45 minutes. In order to complete the transformation the irradiation was continued for another 45 minutes at 80 C. For the workup, the reaction mixture was quenched with a solution of citric acid (10%), then extracted with ethyl acetate (5×30 ml) followed by a 20:80-mixture of methanol and dichloromethane (200 ml). The combined organic layers were dried over sodium sulphate, evaporated at reduced pressure and, finally, lyophilized to remove residual dimethylsulphoxide. Further purification by flash chromatography on silica gel yielded the 5-cyclopropylmethoxy-pyrazine-2-carboxylic acid as an off-white solid (1.83 g, 27% of theory). MS (ISP): m/z=195 [M+H]+.

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, 5-Chloropyrazine-2-carboxylic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; Banner, David; Guba, Wolfgang; Hilpert, Hans; Mauser, Harald; Mayweg, Alexander V.; Narquizian, Robert; Pinard, Emmanuel; Power, Eoin; Rogers-Evans, Mark; Woltering, Thomas; Wostl, Wolfgang; US2011/144097; (2011); A1;,
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4430-75-5, name is Octahydro-2H-pyrido[1,2-a]pyrazine, belongs to pyrazines compound, is considered to be a conventional heterocyclic compound, which is widely used in drug synthesis. The chemical synthesis route is as follows. name: Octahydro-2H-pyrido[1,2-a]pyrazine

EXAMPLE 84 5-(3,4-Dimethoxybenzylamino)-2-(2-furyl)-8-(1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazin-2-ylmethyl)[1,2,4]triazolo[1,5-c]pyrimidine (Compound 84) The subject compound (92%) was obtained as a pale brown oily matter from 5-(3,4-dimethoxybenzylamino)-8-formyl-2-(2-furyl)[1,2,4]triazolo[1,5-c]pyrimidine and 1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazine in a manner similar to that in Example 1. 1H NMR (CDCl3, delta, ppm): 1.24-1.26 (m, 2H), 1.48-1.51 (m, 2H), 1.70-1.73 (m, 2H), 2.06-2.09 (m, 4H), 2.35-2.39 (m, 1H), 2.78-2.96 (m, 4H), 3.83 (s, 2H), 3.89 (s, 3H), 3.89 (s, 3H), 4.76 (d, J=5.6 Hz, 2H), 6.40 (t, J=5.6 Hz, 1H), 6.56 (dd, J=1.8, 3.6 Hz, 1H), 6.85 (d, J=8.1 Hz, 1H), 6.95 (s, 1H), 6.97 (d, J=8.1 Hz, 1H), 7.21 (d, J=3.5 Hz, 1H), 7.59 (d, J=1.8 Hz, 1H), 7.92 (s, 1H)

The synthetic route of 4430-75-5 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Uesaka, Noriaki; Imma, Hironori; Kashima, Hajime; Kurokawa, Masako; Nonaka, Hiromi; Kanda, Tomoyuki; Kuwana, Yoshihisa; Toki, Shinichiro; Shimada, Junichi; US2004/110826; (2004); A1;,
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Pyrazine | C4H4N2 – PubChem

Synthetic Route of 6705-33-5, 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. 6705-33-5, name is Pyrazin-2-ylmethanol belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

1 eq. Preparation 2a, 2 eq. of pyrazin-2-ylmethanol and 2 eq. triphenylphosphine were dissolved in dry toluene (0.2M for the phenol), then 2 eq. DTAD was added. The mixture was stirred at 50 C under nitrogen atmosphere. After reaching an appropriate conversion the volatiles were removed under reduced pressure. The crude intermediate was purified via flash chromatography using heptane and EtOAc as eluents to obtain ethyl (2R)-2- acetoxy-3-[2-(pyrazin-2-ylmethoxy)phenyl]propanoate.

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

Reference:
Patent; LES LABORATOIRES SERVIER; VERNALIS (R&D) LIMITED; BALINT, Balazs; CSEKEI, Marton; SZABO, Zoltan; SZLAVIK, Zoltan; KOTSCHY, Andras; CHANRION, Maia; GENESTE, Olivier; CHEN, I-Jen; DAVIDSON, James Edward Paul; MURRAY, James Brooke; SIPOS, Szabolcs; ONDI, Levente; PROSZENYAK, Agnes; (164 pag.)WO2016/207217; (2016); A1;,
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Pyrazine | C4H4N2 – PubChem

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. 6863-73-6, name is 3-Chloropyrazin-2-amine, A new synthetic method of this compound is introduced below., SDS of cas: 6863-73-6

General procedure: Sodium hydride (60% in mineral oil, 0.04 g, 1 mmol) was addedto a stirred solution of benzyl alcohol derivative (1 mmol) inanhydrous N,N-dimethylformamide (3 mL of DMF) at room temperatureand stirring was continued for 1 h. 2-Amino-3-chloropyrazine (8b, 0.13 g, 1 mmol) was added to the reactionmixture and the reaction mixture was stirred at 100 C for 15 h.After cooling, the solvent was evaporated and the residue waspartitioned betweenwater and dichloromethane. The organic layer was dried over sodium sulfate anhydrous, filtered, and concentrated.The residue was purified by column chromatography (SiO2,EA/n-Hex 1/5). 4.1.2.1 3-(Benzyloxy)pyrazin-2-amine (9g) Yellow solid, yield: 53.8%, 1H NMR (400?MHz, CDCl3) delta?=?5.45 (2H, s, OCH2Ph), 6.20 (2H, br, NH2), 7.38-7.48 (7H, m, ArH). Reported [ 48,49].

The synthetic route of 6863-73-6 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Elkamhawy, Ahmed; Park, Jung-eun; Hassan, Ahmed H.E.; Pae, Ae Nim; Lee, Jiyoun; Park, Beoung-Geon; Roh, Eun Joo; European Journal of Medicinal Chemistry; vol. 144; (2018); p. 529 – 543;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 89123-58-0,Some common heterocyclic compound, 89123-58-0, name is 5-Bromopyrazine-2,3-diamine, molecular formula is C4H5BrN4, 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.

(3-((tert-butyldimethylsilyl)oxy)-4-cyclohexyl-2-fluorophenyl)boronic acid (0.821 g, 2.33 mmol), 5-bromopyrazin-2-amine (0.40 g, 2.3 mmol), K2CO3 (0.659 g, 4.77 mmol), Pd(dppf)Cl2.CH2Cl2 (0.086 g, 0.12 mmol), deoxygenated toluene (10 mL), and deoxygenated deionized water (10 mL) was heated for 16 hours at 80 Celsius. The reaction mixture was then cooled to rt, diluted with dichloromethane (25 mL), and washed with brine (2×25 mL). The organic layer was dried over MgSO4, filtered, and concentrated to dryness to yield the title compound (0.936 g, 100%) which was used without purification.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 5-Bromopyrazine-2,3-diamine, its application will become more common.

Reference:
Patent; JANSSEN PHARMACEUTICA NV; Eccles, Wendy; Fitzgerald, Anne E.; Hack, Michael D.; Hawryluk, Natalie A.; Jones, William M.; Keith, John M.; Krawczuk, Paul; Lebsack, Alec D.; Liu, Jing; Mani, Neelakandha S.; McClure, Kelly J.; Meduna, Steven P.; Rosen, Mark D.; US2014/221310; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 1174321-06-2, 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. 1174321-06-2, name is 5-(Difluoromethyl)pyrazine-2-carboxylic acid belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

5-(Difluoromethyl)pyrazine2carboxylic acid (30.0 g, 1.05 equiv) and (4aS,5S,7aS)-7a-(5-amino-2-fluorophenyl)-5-fluoromethyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-amine (49.2 g, 1.00 equiv.) were charged to a reactor and EtOAc (443 mL) was added to the mixture to give a suspension. A solution of T3P (105 g 1.10 equiv, 50 wt% in EtOAc) (Archimica, Germany) was added at ambient temperature while controlling the internal temperature below 30 C. The reaction mixture was stirred at 4045 C >3 hours and monitored by HPLC. The reaction mixture was cooled to ambient temperature and water (98 mL) was charged. After 1015 minutes charged 28% ammonium hydroxide (137 mL) while controlling the temperature below 30 C. Additional EtOAc (172 mL) was added and the reaction mixture was stirred for 30 minutes at ambient temperature. The aqueous phase was separated and backextracted with EtOAc (246 mL). The organic phases were combined and washed with 15% aq. NaCl (98 mL) and water (98mL). The organic layer was filtered over Celite (0.5 Wt) and concentrated under vacuum to obtain a beige solid (quantitative crude yield) which was recrystallized from 1propanol to afford N-(3-((4aS,5S,7aS)-2-amino-5-(fluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-7a-yl)-4-fluorophenyl)-5-(difluoromethyl)pyrazine-2-carboxamide as a tan solid (54.2g).

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, 5-(Difluoromethyl)pyrazine-2-carboxylic acid, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; ???????????????????????????; ? Buranko; Kimu ?; Chan ?; ?; Yoshizawa Kazuhiro; (94 pag.)JP2016/121177; (2016); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 486460-21-3, 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 486460-21-3 as follows.

Anhydrous DMF and N-ethyl-N-isopropylpropan-2-amine (20.88 mg, 0.162 mmol)were added to a mixture of HATU (28.7 mg, 0.075 mmol), HOAT (10.3 mg, 0.075 mmol), 1-(6-chloro-3-cyanoquinolin-4-yl)piperidine-4-carboxylic acid (17 mg, 0.054 mmol) and 3-(trifluoromethyl)-5 ,6,7, 8-tetrahydro- [1 ,2,4jtriazolo[4,3 -aj pyrazine (12.3 mg, 0.054 mmol).The mixture was stirred at room temperature for 6 hours. The reaction mixture was pouredinto 10 ml NaHCO3 aqueous solution, and the resulting suspension was stirred for 1 hour.The mixure was filtered and the filter cake was washed with water, and dried to afford the title compound.MS: 490 (M + 1). Human CYP8B1 1C50 (nM) 23.2

According to the analysis of related databases, 486460-21-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; MERCK SHARP & DOHME CORP.; CUMMING, Jared, N.; DYKSTRA, Kevin, D.; HRUZA, Alan; LI, Derun; LIU, Hong; TANG, Haiqun; TAOKA, Brandon, M.; VERRAS, Andreas; WALSH, Shawn, P.; WU, Wen-Lian; (170 pag.)WO2018/34918; (2018); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 6905-47-1, 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. 6905-47-1, name is 2-Amino-6-methoxypyrazine, This compound has unique chemical properties. The synthetic route is as follows.

To a solution of 6-methoxypyrazin-2-amine (3 g, 24 mmol) in dry DMF (35 mL), N-chlorosuccinimide (3.2 g, 24 mmol) was added. The reaction mixture was stirred at room temperature for 16 h then waspoured into ice and brine (130 mL). The aqueous solution was extracted with ethyl acetate (3 x 120 mL), the organic phase was washed with 5% solution of LiCI, dried over Na2SO4 and evaporated under reduced pressure. The crude was purified by SNAP-340-NH (cyclohexane/ethyl acetate from 95:5 up to 8:2) and by SNAP1 00-Si-OH (eluting with DCM)to afford the title intermediate (1.98 g, 12.5 mmol, 52% yield). LC-MS (M-H) = 160.1

The chemical industry reduces the impact on the environment during synthesis 2-Amino-6-methoxypyrazine. I believe this compound will play a more active role in future production and life.

Reference:
Patent; AZIENDE CHIMICHE RIUNITE ANGELINI FRANCESCO A.C.R.A.F. S.P.A.; OMBRATO, Rosella; MAGARO’, Gabriele; GAROFALO, Barbara; FURLOTTI, Guido; MANGANO, Giorgina; CAPEZZONE DE JOANNON, Alessandra; (182 pag.)WO2017/211759; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 912773-24-1, These common heterocyclic compound, 912773-24-1, name is 6-Bromoimidazo[1,2-a]pyrazine, 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 : To a solution of 6-bromoimidazo [1, 2-a] pyrazine (30 g, 151 mmol) in toluene (400 mL) were sequentially added Cs2C03 (123 g, 378 mmol), 4-(ethoxycarbonyl)phenylboronic acid (35.2 g, 181 mmol) and Pd(dppf)2Cl2 (3.70 g, 4.50 mmol). The reaction mixture was stirred at 90 C for 12 h under argon atmosphere then, was filtered through celite. The filtrate was concentrated and the residue was purified the by flash column chromatography (silica gel, eluent n-hexane/EtOAc 70:30) to afford ethyl 4-(imidazo [1, 2-a]pyrazin-6-yl)benzoate (16 g, 39%) as yellow solid. 1H NMR (400 MHz, DMSO-i 6) 5: 9.35 (s, IH), 9.17 (s, IH), 8.15 (d, J= 8.4 Hz, 2H), 8.03 (d, J= 8.4 Hz, 2H), 7.88 (s, IH), 7.79 (s, IH), 4.32 (q, J= 6.8 Hz, 2H), 1.44 (t, J = 7.2 Hz 3H); MS (ESI) m/z 268 [C,5H13N302 ^H] “.

The synthetic route of 912773-24-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH; NACRO, Kassoum; DURAISWAMY, Athisayamani, Jeyaraj; CHENNAMANENI, Lohitha, Rao; WO2013/147711; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem