Month: August 2021

Synthetic Route of 5049-61-6, 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. 5049-61-6, name is Pyrazin-2-amine, This compound has unique chemical properties. The synthetic route is as follows.

3,5-Dibromopyrazin-2-amine Pyrazin-2-amine (2.0g, 21 mmol) was dissolved in dichloromethane (50 mL)and the resulting solution was stirred at room temperature. N-bromosuccinimide(9.4g, 53mmol) was added. After completion, the mixture was concentrated underreduced pressure to give brown solid crude which was subsequently purified bychromatography (applied in hexane; eluted 10% EtOAc/hexane) to give the title compound as a pale yellowsolid (3.6g 14 mmol, 68%). Mpt: 106-108 oC; Rf = 0.80 (1:1 EtOAc/hexane);IR (numax/cm-1, thin film): 3447, 3280, 3154, 1621, 1549,1506, 1450; 1H NMR (600 MHz, CDCl3): deltaH = 5.04(brs, 2H, NH2), 8.04(s, 1H, 6-H); 13C NMR(150 MHz, CDCl3): deltaC = 123.8 (C-5), 124.0 (C-3),143.3 (C-6), 152.0 (C-2); HRMS m/z (CI+): found251.87731 [M+H]+, C4H4Br2N3requires 251.87720.

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

Reference:
Article; Sayer, James R.; Walldn, Karin; Pesnot, Thomas; Campbell, Frederick; Gane, Paul J.; Simone, Michela; Koss, Hans; Buelens, Floris; Boyle, Timothy P.; Selwood, David L.; Waksman, Gabriel; Tabor, Alethea B.; Bioorganic and Medicinal Chemistry; vol. 22; 22; (2014); p. 6459 – 6470;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 23229-26-7, 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 23229-26-7 as follows.

Step 3: Synthesis of 2-bromo-5-(methylthio)pyrazine To a stirred solution of 2,5-dibromopyrazine (0.45 g, 1.892 mmol) in anhydrous THF (5 mL) was added 21% aq. solution of sodium thiomethoxide (0.94 mL g, 2.83 mmol) at 0 C. and stirred for 1 h at RT. Progress of reaction was monitored by TLC. After reaction completion DCM was added and washed with water. The organic layer was dried over sodium sulphate and concentrated under reduced pressure to yield 2-bromo-5-(methylthio)pyrazine (0.3 g, 78%) as brown oil. MS: 206.08 [M++1]

According to the analysis of related databases, 23229-26-7, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Mankind Pharma Ltd.; Patil, Rakesh Ishwar; Verma, Jeevan; Shah, Dharmesh; Ali, Sazid; Bapuram, Srinivasa Reddy; Rai, Santosh Kumar; Kumar, Anil; (146 pag.)US2017/291910; (2017); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 59489-71-3, These common heterocyclic compound, 59489-71-3, name is 2-Amino-5-bromopyrazine, 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 solution of 5-bromopyrazinamine (3.0 g, 17.2 mmol, 1.0 equiv) in HI ( 1 1.1 mL, 57% in water) at 00C was slowly added I2 (3.0 g, 24.1 mmol, 0.7 equiv) over 1 hr, followed by addition OfNaNO2 (5.0 g, 145 mmol, 4.2 equiv) over a period of 3 hr at 0 0C. The reaction mixture was made alkaline by first adding 10% Na2S2Os solution (150 mL), then saturated Na2COs solution (90 mL). The mixture was extracted with diethyl ether (3 x 250 mL). The organic layer was washed with 10% Na2S2Os solution, dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by column chromatography [SiO2, ethyl acetate/hexanes, 0:100 to 10:90, v/v] to give 2-bromo-5- iodo-pyrazine (1.6 g, 32%). 1H NMR (400 MHz, CD2Cl2) delta 8.62 (s, IH), 8.51 (s, IH).

The synthetic route of 59489-71-3 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; NOVARTIS AG; NOVARTIS PHARMA GmbH; XENON PHARMACEUTICALS INC; WO2008/24390; (2008); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 767340-03-4,Some common heterocyclic compound, 767340-03-4, name is (2Z)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-2-amine, molecular formula is C16H13F6N5O, 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 solution of ( Z) -4-oxo-4- [3-(trif luoromethyl) -5, 6-dihydro [1,2,4] triazolo[4,3-a] pyrozin- 7 (8H) -yl] -l-(2, 4, 5-trifluorophenyl) -but-2-en-2-amine (2.00 g,4.94 mmol) and triethyl amine (1.0Og, 9.88 mmol) in dichloromethene (100 mL) was added Boc anhydride (2.15g,9.85 mmol) . The reaction mixture was stirred at reflux for40 h. Concentration was followed by purification by flash chromatography to afford 1.24 g of product (49.8percent) . 1H NMR(400 MHz, d6-DMSO) 11.27 (s, IH) 7.56-7.50 (m, IH), 5.63 (s,IH), 5.00-4.94 (m, 2H), 4.06-4.00 (m, 4H), 1.35 (s, 9H) .

The synthetic route of 767340-03-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; CHIRAL QUEST, INC.; WU, Shulin; YU, Bo; WANG, Yejing; DELICE, Alain; ZHU, Jingyang; WO2010/78440; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 939412-86-9, A common heterocyclic compound, 939412-86-9, name is (3-Chloropyrazin-2-yl)methanamine hydrochloride, molecular formula is C5H7Cl2N3, 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 mixture of (trans)-6-oxooctahydro-l H-quinolizine-3 -carboxylic acid (520 mg, 2.64 mmol), (3-chloropyrazin-2-yl)methanamine hydrochloride (570 mg, 3.17 mmol), HATU (1.50 g, 3.95 mmol) and TEA (0.79 g, 7.91 mmol) in DCM (13 mL) was stirred at 25 C overnight. The mixture was quenched with H20 (40 mL) and extracted with DCM (15 mL*3).The combined organic layerswere dried over anhydrous sodium sulfate, filtered and concentrated to give a crude product.The crude product was purified by column chromatography on silica gel eluting with PE / THF (0-60%) to give (trans)- N-((3-chloropyrazin-2-yl)methyl)-6-oxooctahydro-l H-quinolizine-3 -carboxamide (0.7 g, 82.35%) as a light yellow solid. 1H NMR (400MHz, CDC13) delta = 8.53 – 8.41 (m, 1H), 8.33 (d, J=2.5 Hz, 1H), 6.96 (br. s., 1H), 5.08 – 4.88 (m, 1H), 4.73 – 4.61 (m, 2H), 3.40 – 3.26 (m, 1H), 2.72 – 2.57 (m, 1H), 2.47 – 2.28 (m, 3H), 2.12 – 2.00 (m, 2H), 1.89 – 1.77 (m, 4H), 1.73 – 1.62 (m, 1H), 1.58 – 1.47 (m, 1H).

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; MERCK SHARP & DOHME CORP.; WU, Hao; KIM, Ronald M.; LIU, Jian; GAO, Xiaolei; BOGA, Sobhana Babu; GUIADEEN, Deodialsingh; LIU, Shilan; YANG, Chundao; WANG, Hongjian; WO2014/113932; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 33332-28-4, name is 2-Amino-6-chloropyrazine, 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 33332-28-4, Recommanded Product: 33332-28-4

2,6-Dichloropyrazine (2.89 g, 19.4 mmol) was stirred in aqueous NH3 (28percent, 10 ml.) and heated to 100°C in a sealed tube for 18 hours. The reaction mixture was cooled and the resultant precipitate was filtered. Trituration with water and then ether gave 6- chloropyrazin-2-amine as a white solid (2.28 g, 17.6 mmol, 91 percent yield). 1H NMR (d6-DMSO, 400 MHz) ? 6.9 (brs, 2H), 7.70 (d, J = 0.4, 1 H), 7.80 (d, J = 0.4, 1 H); LC-MS (ZQ, 6 minutes) Rt = 1.05 minutes; m/z (ESI+) 130 (M+H).6-Chloropyrazin-2-amine (2.50 g, 19.3 mmol) was stirred in CH2CI2 (60 ml.) at 0°C.A/-Bromosuccinimide (2.92 g, 16.4 mmol) was added slowly and the reaction mixture was stirred at 0°C for 60 minutes. The reaction mixture was filtered through celite and concentrated to give a brown oil. Purification by flash chromatography, eluting with 0-25percent EtOAc-hexanes, gave 5-bromo-6-chloropyrazin-2-amine as a yellow solid (1 .69 g, 8.16 mmol, 42percent yield). 1H NMR (de-DMSO, 400 MHz) ? 7.1 (brs, 2H), 7.65 (s, 1 H); LC-MS (ZQ, 4 minutes) Rt = 1.46 minutes; m/z (ESI-) 205 (M-H).A mixture of 5-bromo-6-chloropyrazin-2-amine (1 .00 g, 4.8 mmol), copper (I) iodide (914 mg, 4.8 mmol), 18-crown-6 (95 mg, 0.36 mmol) andtetrakis(triphenylphosphine)palladium (0) (83 mg, 0.072 mmol) was suspended in dry DMF (20 ml.) and a stream of nitrogen was passed through for 5 minutes. Potassium cyanide (312 mg, 4.8 mmol) was added and the mixture was stirred at room temperature for 30 minutes, then refluxed at 200°C for 3 hours. The mixture was cooled, diluted with EtOAc and absorbed onto silica gel (10 g). DMF was removed by evaporation. The product was purified by flash chromatography, eluting with 1 :1 EtOAc-hexanes, to yield 5- amino-3-chloropyrazine-2-carbonitrile as a yellow solid (607 mg, 3.93 mmol, 82percent yield). 1H NMR (d6 DMSO, 400 MHz) ? 7.87 (s, 1 H), 8.1 (brs, 2H); LC-MS (ZQ, 4 minutes) Rt = 1.20 minutes; m/z (ESI-) 153 (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, 2-Amino-6-chloropyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; CANCER RESEARCH TECHNOLOGY LIMITED; COLLINS, Ian; LAINCHBURY, Michael; MATTHEWS, Thomas Peter; READER, John Charles; WO2013/68755; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

78342-42-4, name is (S)-2,5-Dihydro-3,6-dimethoxy-2-isopropylpyrazine, 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. SDS of cas: 78342-42-4

To a solution of 3.32 g (18 mmol) of commercially available (2S)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine in 100 mL of tetrahydrofuran at ?70° C. was added 12 mL (19 mmol) of a 1.6M solution of butyllithium in hexanes. After stirring at this temperature for 20 min, 5 g (19.5 mmol) of 2-fluoro-4-trifluoromethylbenzyl bromide in 20 mL of tetrahydrofuran was added and stirring was continued for 3 h before warming the reaction to ambient temperature. The reaction was quenched with water, concentrated in vacuo, and extracted with ethyl acetate. The combined organic phase was washed with brine, dried, and concentrated in vacuo. Purification by flash chromatography (silica gel, 0-5percent ethyl acetate in hexanes) afforded 5.5 g of the title compound. 1H NMR (500 MHz, CDCl3) delta 7.33-7.25 (m, 3H), 4.35-4.31 (m, 1H), 3.75 (s, 3H), 3.65 (s, 3H), 3.60 (t, 1H, J=3.4 Hz), 3.33 (dd, 1H, J=4.6, 13.5 Hz), 3.03 (dd, 1H, J=7, 13.5 Hz), 2.25-2.15 (m, 1H), 1.0 (d, 3H, J=7 Hz), 0.66 (d, 3H, J=7 Hz)

The synthetic route of 78342-42-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Merck Sharp & Dohme Corp.; Edmondson, Scott D.; Fisher, Michael H.; Kim, Dooseop; Maccoss, Malcolm; Parmee, Emma R.; Weber, Ann E.; Xu, Jinyou; US2015/359793; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 153800-11-4, 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 153800-11-4 as follows.

(+)-((2R,3R,4S,5R,6S)-3-Acetoxy-6-(((3R,4R,5S)-5-azido-4-hydroxytetrahydro- 2//-pyran-3-yl)thio)-5-methoxy-4-(4-(3,4,5-trifluorophenyl)-li/-l,2,3-triazol-l- yl)tetrahydro-2 /-pyran-2-yl)methyl acetate (62 mg, 0.101 rnmol) and 2-ethynylpyrazine (16.75 mg, 0.161 mmol) were dissolved in a previously degassed solution of DMF (3 mL) and water (1.000 ml) and the mixture was placed under argon. Sodium ascorbate (23.90 mg, 0.121 mmol) and copper(II) sulfate pentahydrate (35.2 mg, 0.141 mmol) (predissolved in 0.5 rnL water) were added and the reaction mixture was stirred at room temperature for 14 h. The mixture and the solid clinging to the stir bar were dissolved by the addition of dichloromethane and methanol. Water (10 mL) and saturated aqueous sodium bicarbonate (10 mL) were added resulting in the formation of a precipitate. The mixture was filtered through a pad of Celite and the filter cake was rinsed with 5% methanol in dichoromethane. The filtrate was transferred to a separatory funnel . Brine (1(3 mL) was added and the aqueous layer was extracted (with gentle shaking) with 5% methanol in dichloromethane (4 x 15 mL). The combined organic layers were washed with brine (15 mL). The organic layer was dried over MgS04, filtered, and concentrated. The product was purified by column chromatography on silica gel (30% ethyl acetate containing 5% methanol/ hexanes 100% ethyl acetate containing 5% methanol/hexanes; 24 g column) to afford ((2R,3R,4S,5R,6S)-3-acetoxy-6-(((3R,4R,5S)-4-hydroxy-5-(4-(pyrazin-2-yl)-l /7-l ,2,3-triazol-l-yl)tetrahydro-2i7-pyran-3-yl)thio)-5- methoxy-4-(4~(3,4,5-trifluorophenyl)-li/-L2,3~triazoi-l-yl)tetrahydro-2/f-pyran~2- yl)m ethyl acetate (65 mg, (3 09(3 mmol, 90% yield) as a white solid. 41 NMR (4(30 MHz, CHLOROFORMS) d 9.44 (d, 7=0.8 Hz, 1H), 8.55 (s, 2H), 8.35 (s, 1H), 7.83 (s, 1H), 7.47 (dd, .7=8.0, 6 5 Hz, 2H), 5.51 (d, 7=2.8 Hz, H I ), 4.74 – 4.64 (m, 2H), 4 62 – 4 52 (m, 1H), 4.40 (dd, 7=11.5, 5.0 Hz, 1H), 4.32 (dd, 7=11.8, 5.0 Hz, 1 1 1). 4.26 (t, 7=9.9 Hz, 1H), 4.20 – 4.09 (m, 4H), 4 09 – 4 03 (m, 1 H), 3.52 (t, 7=1 1.9 Hz, 1H), 3 36 (s, 3H), 3 17 (ddd. 7=1 1 .8, 9.8, 5.0 Hz, i l l ), 2.1(3 (s, 31 1 ), 1.94 (s, 3H); 1.C7MS (ESI) mie 721 .2 [(M+H)+, calcd for CsoHxrFsNsOgS 721.2], /R = 1.88 min (Method 2).

According to the analysis of related databases, 153800-11-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; HARTZ, Richard A.; XU, Li; YOON, David S.; REGUEIRO-REN, Alicia; JALAGAM, Prasada Rao; PANDA, Manoranjan; NAIR, Satheesh Kesavan; (171 pag.)WO2019/241461; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 24241-18-7,Some common heterocyclic compound, 24241-18-7, name is 2-Amino-3,5-dibromopyrazine, molecular formula is C4H3Br2N3, 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.

[00183] A mixture of 3,5-dibromopyrazin-2-amine (214 mg, 0.83 mmol) and phenyl boronic acid (100 mg, 0.8 mmol) in toluene (8 mL) was degassed and backfilled with nitrogen 3 times. Pd(PPtLs)4 (46 mg) was added followed by 2M K3PO4 (0.8 mL) and EtOH (1 mL). The mixture was heated at reflux for 18 h. The solution was cooled to room temperature, partitioned between EtOAc (25 mL) and water (5 mL). The layers were separated and the organic layer dried over Na2SO4, filtered and concentrated to an oil which was purified via silica gel chromatography (15% EtOAc/heptane) to afford the product (187 mg, 95% yield).

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

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; WO2009/155389; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 23688-89-3, name is 6-Chloropyrazine-2-carboxylic acid, molecular formula is C5H3ClN2O2, 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. COA of Formula: C5H3ClN2O2

(R)-(2,2-dimethyl-1,3-dioxolan-4-yl)methanol (2.50 g, 18.93 mmol) was added to a room temperature suspension of NaH 60 wt% (833.0 mg, 20.82 mmol) in THF (50 mL). The reaction mixture was stirred at room temp for 30 min and a solution of 6-chloropyrazine-2-carboxylic acid (1.0 g, 6.31 mmol) in THF (20 mL) was added. The reaction mixture was stirred at room temp for 30 min then heated at reflux for 2 h. After cooling to room temp, the pH was adjusted to 3 by the addition of 3 N HCl (4 mL). The mixture was poured into brine and extracted with EtOAc. The combined organics were dried and concentrated. The crude product was recrystallized from pentane/EtOAc to give (R)-6-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)pyrazine-2-carboxylic acid (764.0 mg, 48% yield). MS (ESI) calcd for C11Eta14Nu2O6(m/z): 254.09; found: 255 [M+H]

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 23688-89-3, its application will become more common.

Reference:
Patent; SIRTRIS PHARMACEUTICALS, INC.; CASAUBON, Rebecca, L.; NARAYAN, Radha; OALMANN, Christopher; VU, Chi, B.; WO2013/59587; (2013); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem