Month: July 2021

Application of 1196152-38-1,Some common heterocyclic compound, 1196152-38-1, name is 2-Bromo-5-(trifluoromethyl)pyrazine, molecular formula is C5H2BrF3N2, 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.

[((1R,4S,6R)-3-{[6-methyl-3-(2-pyrimidinyl)-2-pyridinyl]carbonyl}-3-azabicyclo[4.1.0]hept-4-yl)methyl]amine D25 (80 mg) and 2-bromo-5-(trifluoromethyl)pyrazine (67.4 mg, 0.297 mmol) were dissolved in DMF (2 ml) then sodium carbonate (52.4 mg, 0.495 mmol) was added and the mixture was heated to 50 C. for 2 hours. DMF was evaporated under vacuum and the residue was dissolved in DCM (4 ml) and washed with NaHCO3 saturated solution (4 ml). The organic phase was filtered through a phase separator tube, concentrated under vacuum and the resulting crude product was purified by SCX Chromatography (column size 5 g). Another purification was performed by silica -NH chromatography (Biotage SP-column size 25 g using Cy_EtOAc=5:5 to EtOAc as eluent). It was recovered the title compound E45 (30 mg). UPLC: (Acid Final_QC): rt=0.78 and 0.79 minutes (two rotamers), peaks observed: 470 (M+1). C23H22F3N7O requires 469. 1H NMR (400 MHz, DMSO-d6) delta ppm 8.91-8.82 (m, 2H), 8.36 (d, 1H), 8.20-7.86 (m, 3H), 7.47 (t, 1H), 7.36 (d, 1H) 4.40 (d, 1H), 3.81-3.55 (m, 2H), 3.49-3.35, (m, 2H), 2.38-2.30 (br. s., 3H), 1.80-1.65 (m, 2H), 1.15-1.06 (m, 1H), 1.03-0.91 (m, 1H), 0.80-0.71 (m, 1H), 0.29-0.19 (m, 1H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Bromo-5-(trifluoromethyl)pyrazine, its application will become more common.

Reference:
Patent; ALVARO, Giuseppe; Amantini, David; Castiglioni, Emiliano; Di Fabio, Romano; Pavone, Francesca; US2010/144760; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 110223-15-9, 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. 110223-15-9, name is 2-Amino-3-benzyloxypyrazine, This compound has unique chemical properties. The synthetic route is as follows.

General procedure: For aromatic urea derivatives; the appropriate aromatic isocyanate(3.0 mmol) was added to a solution of the appropriate 2-amino-3-benzyloxy pyrazine derivative (2.5 mmol) in THF(10 mL). The reaction was refluxed for 3e6 h. After cooling, thereaction mixture was evaporated and the residue was purified byprecipitation in cold methanol and filtered to give the targetcompound(s). For aliphatic urea derivatives; the appropriatealiphatic isocyanate derivative (1.02 mmol) was added to a solutionof the appropriate 2-amino-3-benzyloxy pyrazine derivative(0.85 mmol) in dry THF (5 mL) in the presence of NaH (60% inmineral oil, 68 mg, 1.71 mmol). The reaction was refluxed for 5 h.After cooling, the reaction mixture was evaporated and the residuewas purified by flash column chromatography (SiO2, EA/n-Hex 1/4).

The chemical industry reduces the impact on the environment during synthesis 2-Amino-3-benzyloxypyrazine. I believe this compound will play a more active role in future production and life.

Reference:
Article; Elkamhawy, Ahmed; Park, Jung-eun; Hassan, Ahmed H.E.; Pae, Ae Nim; Lee, Jiyoun; Paik, Sora; Park, Beoung-Geon; Roh, Eun Joo; European Journal of Medicinal Chemistry; vol. 157; (2018); p. 268 – 278;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 6705-33-5, A common heterocyclic compound, 6705-33-5, name is Pyrazin-2-ylmethanol, molecular formula is C5H6N2O, 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.

General procedure: These compounds were synthesized according to previously reported method.4 28a was purchased from commercial sources and used as received. To a solution of 27a-27c (1.0 mmol) in Et2O (10 mL) was added 60% NaH (1.0 mmol). The reaction mixture was stirred at rt for 10 min before adding trichloroacetonitrile (1.0 mmol) at once. The resulting solution was stirred for 2-5 h and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography to yield the desired compounds 28a-28c.

The synthetic route of 6705-33-5 has been constantly updated, and we look forward to future research findings.

Reference:
Article; Xu, Yulong; Yang, Xicheng; Chen, Yiyi; Chen, Hao; Sun, Huijiao; Li, Wei; Xie, Qiong; Yu, Linqian; Shao, Liming; Bioorganic and Medicinal Chemistry Letters; vol. 28; 12; (2018); p. 2148 – 2152;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 243472-70-0, A common heterocyclic compound, 243472-70-0, name is 5-Bromo-2,3-diphenylpyrazine, molecular formula is C16H11BrN2, 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.

The reaction flask was charged with 5-bromo-2,3-diphenylpyrazine (100 g, 0.32 mol)4-Isopropylamino-1-butanol (127 g, 0.96 mol) andPotassium iodide (15.9 g, 0.096 mol) was added and the mixture was heated to 150 C for 16 hours.After the system was cooled to room temperature, ethyl acetate (800 mL)Washed with water (800 mL × 2), dried over anhydrous sodium sulfate, filtered,The filtrate was concentrated under reduced pressure and the residue treated with dichloromethane / heptane (1.2 L, v / v = 1: 5)Recrystallization, get4 – ((5,6-diphenylpyrazin-2-yl) – (isopropyl) amino) -1-butanol(75.5 g, yield: 65.3%).

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; Hangzhou East China Pharmaceutical Group New Drug Institute Co., Ltd.; Zhang Qianqian; Qu Xiaoxia; (14 pag.)CN107365275; (2017); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – 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. 6966-01-4, name is Methyl 3-amino-6-bromopyrazine-2-carboxylate, This compound has unique chemical properties. The synthetic route is as follows., category: Pyrazines

(iv) 3-Amino-6-bromopyrazine-2-carboxylic acid: To a solution of the product of step (iii) (200 g, 0.86 mol) in MeOH (500 mL) was added 5 N-NaOH (500 mL) slowly. The resulting mixture was stirred at 50 C for 3 hours. MeOH was removed under a reduced pressure and water (300 mL) added to the reaction mixture. The solution was acidified to pH 3 with 6N-HC1. The solution was extracted with EtOAc and washed with water. The combined organic extract was dried over Na2S04, filtered and evaporated to dryness to afford the subtitle compound (iv) as a brown yellow solid (180 g). 1H-NMR (400 MHz, CDC13) delta 8.30 (s, 1H);HPLC Retention Time = 0.850min.

According to the analysis of related databases, 6966-01-4, the application of this compound in the production field has become more and more popular.

Reference:
Patent; ASTRAZENECA AB; ASTRAZENECA UK LIMITED; FENG, Tao; SANGANEE, Hitesh, Jayantilal; WADA, Hiroki; WO2011/89416; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 33332-28-4, 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. 33332-28-4, name is 2-Amino-6-chloropyrazine, This compound has unique chemical properties. The synthetic route is as follows.

[l-(tert-butoxycarbonyl)-lH-indol-2-yl]boronic acid (2.22 g, 8.49 mmol), 6- chloropyrazin-2-amine (1.00 g, 7.72 mmol), K2CO3 (2.67 g, 19.3 mmol) and Pd(PPh3)4 (180 mg, 0.15 mmol) were mixed in MeCN/water (3.5: 1) and stirred at 85 0C for 20 hours. The reaction mixture was concentrated and the residue was extracted with EtOAc (2x 40 mL) and water (50 mL). The organic layers were combined, dried (Na2SO^, filtered and concentrated to give 2.5 g of a brown solid of tert-butyl 2-(6-aminopyrazin-2-yl)- lH-indole-l-carboxylate. The material was used in the next step without further purification. To tert-butyl 2-(6-aminopyrazin-2-yl)-lH-indole- l-carboxylate (1.1 g, 3.5 mmol) in dry toluene (10 mL) were added methyl 6-chloronicotinate (0.67 g, 3.90 mmol), K2CO3 (7.35 g, 53.2 mmol), (+/-)-BINAP (0.1 1 g, 0.18 mmol) and Pd(OAc)2 (40 mg, 0.18 mmol). The mixture was re fluxed for 50 minutes. The solvent was evaporated and the residue was extracted with EtOAc (2×100 mL) and washed with water/brine (1 : 1 ; 100 mL). The organic layers were combined, dried (Na2Spsi4), filtered and concentrated to give 2 g of crude product. Purification was performed by flash chromatography (1percent NEt3 in DCM-> 1percent NEt3, 1percent MeOH in DCM). This gave tert-butyl 2-(6-{[5-(methoxycarbonyl)pyridin-2- yl]amino}pyrazin-2-yl)-lH-indole- l-carboxylate (620 mg). The material was divided into four microwave tubes (155 mg, 0.35 mmol in each) and dissolved in MeOH. 2M aq NaOH (0.35 mL, 0.70 mmol) was added and the reaction mixture was irradiated in a microwave oven at 1 10 0C for 15 minutes. 6M aq HCl (0.12 mL, 0.70 mmol) was added. The reactions were combined and concen- trated in vacuo to give the crude title compound as a brown solid (720 mg). MS (ESI+) for C18H 13N5O2 m/z 332 (M+H)+.

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

Reference:
Patent; BIOVITRUM AB (PUBL); WO2007/147874; (2007); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 875781-43-4, 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. 875781-43-4, name is 2-Bromo-5H-pyrrolo[2,3-b]pyrazine belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below.

To a stirred solution of 2-bromo-5H-pyrrolo[2,3-b]pyrazine (from Ark Pharm, cat AK-23813, 1.00 g, 5.05 mmol) in tetrahydrofuran (10 mL), NaH (60% w/w dispersion form in mineral oil, 283 mg, 7.07 mmol) was added at 0 C. After 0.5 hour, benzenesulfonyl chloride (644 muL, 5.05 mmol) was added dropwise. After another 1 hour, the reaction mixture was quenched with saturated aqueous NH4Cl and extracted with methylene chloride. The combined organic layers were dried over MgSO4, filtered, and concentrated. The residue was purified on silica gel (eluting with 0 to 50% ethyl acetate (EtOAc) in hexanes) to give the desired product (1.50 g, 88%). LCMS calculated for C12H9BrN3O2S (M+H)+: m/z=339.2. Found: 339.2.

The synthetic route of 2-Bromo-5H-pyrrolo[2,3-b]pyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Incyte Corporation; Lu, Liang; He, Chunhong; Yao, Wenqing; US2014/45814; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 1196152-38-1, These common heterocyclic compound, 1196152-38-1, name is 2-Bromo-5-(trifluoromethyl)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.

Example 44k (300 mg, 0.8 mmol), 2-Chloro-5-(trifluoromethyl)pyrimidine (199 mg, 1.09 mmol) and N,N-diisopropylethylamine (287 mul, 1.67 mmol) are dissolved in 4 ml of anhydrous DMSO and heated in a microwave reactor during 30 minutes at 150C. The crude is partitioned between EtOAc and water, the organic layer is dried over anhydrous Na2S04 then concentrated under reduced pressure to obtain 360 mg of the title product. HPLC-MS (Method 10): Rt = 3. MS (ES+): m/z = 505 [M+H]+ . The enantiomers are obtained by HPLC using a chiral stationary phase. Method for separation: HPLC apparatus type: Waters 600 Pump; column: Daicel Chiralpack AD-H, 5.0 muiotaeta, 250 mm x 20 mm; method: eluent hexane/ IPA 70:30; flow rate: 15 mL/min, Temperature: 25 C; UV Detection: 254 nm Example of separation by chiral HPLC: Submitted to separation: 665 mg of Example 1 prepared as described above; Obtained: 157 mg of enantiomer 1 (Exp. 2) and 40 mg of enantiomer 2 (Exp. 3). Example 34 is synthesized as described for example 1 starting from example 44f (80 mg, 0.22 mmol) instead of example 44k, 2-Bromo-5-(trifluoromethyl)pyrazine (75 mg, 0.33 mmol) instead of 2-Chloro-5-(trifluoromethyl)pyrimidine, N,N-diisopropylethylamine (75 mu, 0.44 mmol) and 1 ml of anhydrous DMSO. The reaction mixture is heated in a microwave reactor at 130C during 30 minutes. After the work-up, the crude product is purified by Silica gel flash chromatography using cyclohexane/EtOAc 20:80 to 0: 100 as eluent to obtain the title compound (83 mg, 74 % yield). HPLC-MS (Method 5): Rt = 2.96 min MS (APCI+): m/z = 505 [M+H]+ .

Statistics shows that 2-Bromo-5-(trifluoromethyl)pyrazine is playing an increasingly important role. we look forward to future research findings about 1196152-38-1.

Reference:
Patent; BOEHRINGER INGELHEIM INTERNATIONAL GMBH; HOENKE, Christoph; GIOVANNINI, Riccardo; LESSEL, Uta; ROSENBROCK, Holger; SCHMID, Bernhard; WO2015/55698; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 762240-92-6, These common heterocyclic compound, 762240-92-6, name is 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride, 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 250 ml three-necked flask,Add 100 ml of dichloromethane,(3R)-3 tert-Butoxycarbonylamino-4-(2,4,5-trifluorophenyl)-butyric acid (VI) (6.6 g, 0.02 mol) and3-trifluoromethyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride (VII) (4.6 g, 0.02 mol) ,Cool to 0 C with an ice salt bath.Add 1-hydroxybenzotriazole (HOBT) (2.7 g, 0.02 mol),1-ethyl-3-(3-dimethylaminopropyl)carbimide hydrochloride (EDC.HCl) (3.82 g, 0.02 mol),Triethylamine (6 g, 0.03 mol) was added dropwise.Reaction for 24h,The reaction solution was washed twice with 50 ml of distilled water.dry,filter,Concentration gave the crude product (9.62 g, 0.019 mol).The yield was 95%.

The synthetic route of 762240-92-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Zhejiang Yongtai Technology Co., Ltd.; Zhejiang Yongtai Pharmaceutical Co., Ltd.; Zhang Feng; Cheng Xuyang; Tan Xiao; (19 pag.)CN109824546; (2019); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – 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. 957230-70-5, name is 3,6-Dibromopyrazin-2-amine, This compound has unique chemical properties. The synthetic route is as follows., name: 3,6-Dibromopyrazin-2-amine

Specifically for weighing 2-amino-3,6-dibromopyrazine2.53g and NaNO21.38g in a 100ml round bottom flask,425 ml of HBF was slowly added dropwise thereto at 0 C, and the reaction was performed at 20 C for 2 hours.The reaction mixture was washed with water and extracted three times with dichloromethane.The organic phase was collected.The obtained organic phase was purified by silica gel column chromatography,This gave 2,5-dibromo-3-fluoropyrazine.Then, 140 mg of the obtained 2,5-dibromo-3-fluoropyrazine, 523 mg of 4- (diphenylamino) phenylboronic acid pinacol ester, and 119 mg of bis (triphenylphosphine) palladium (II) dichloride were taken.142 mg of tetrabutylammonium bromide was placed in a 50 ml reaction tube, 5 ml of K2CO3 solution (6 mol / L) and 10 ml of toluene were added under N2 protection, and the reaction was performed at 85 C. for 24 h.The reaction product was washed with water and extracted three times with dichloromethane, and the organic phase was collected.Purified by silica gel column chromatography.54 mg of 4,4 ‘-(3-fluoropyrazine-2,5-diyl) bis (N, N-diphenylaniline) was obtained as a yellow solid.

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 957230-70-5.

Reference:
Patent; Xi’an Jiaotong University; Chen Kai; Wu Shuqi; Bian Xiaoli; Wang Qiutang; (12 pag.)CN110540524; (2019); A;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem