Month: July 2021

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. HPLC of Formula: C6H8ClF3N4

General procedure: A solution of 3-(trifluoromethyl)-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyrazine hydrochloride salt 9 (1.0 eq.) in dimethylformamide (DMF, 2e3 mL) was added potassium carbonate (2.5eq.) at 5 C and stirred for 15 min at room temperature. To this,various chloride derivatives (1.0 eq.) in DMF was added to reaction mixture at same temperature. The resultant reaction mixture was allowed to stir at room temperature for 24 h. The completion of the reaction was monitored on TLC (using 10% MeOH: DCM and ammonia as a modifier as mobile phase). The reaction mixture was poured into ice-cold water and extracted with ethyl acetate(2 x 15 mL). Organic layers were combined and the combined organic layer was dried over sodium sulfate and concentrated under reduced pressure to afford crude material and crystallized it from methanol to get 3-(trifluoromethyl)-5,6,7,8-tetrahydro [1,2,4]triazolo [4,3-a]pyrazine derivatives (12f-12j) in good practical yield.

The synthetic route of 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride has been constantly updated, and we look forward to future research findings.

Reference:
Article; Jethava, Divya J.; Acharya, Prachi T.; Vasava, Mahesh S.; Bhoi, Manoj N.; Bhavsar, Zeel A.; Rathwa, Sanjay K.; Rajani, Dhanji P.; Patel, Hitesh D.; Journal of Molecular Structure; vol. 1184; (2019); p. 168 – 192;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 33332-28-4, 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. 33332-28-4 name is 2-Amino-6-chloropyrazine, This 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 29: Preparation of:2-(4-Ch]oro-2-mophiholin-4-yl-1.24hiazol-5-yl)-5-(dicvcloprorhoyImethylV3,7-dimethyl-5H-pyitauolof2.3- ipyrazine; Part A: 2-Amino-6-methy] pyrazine; A solution of zinc chloride (2.0M in THF, 96.5 mL, 48.2 mmol, 5.0 equiv.) is treated dropwise with methylmagnesium bromide (3.0 M in Et2O, 32.2 mL, 96.5 mmoi, 10.0 equiv.) at 0 °C. The mixture is wanned to room temp and stirred for 45 min. A solution of 2-amino-6-chloro pyrazine (1.25 g. 9.65 mmol, 1.0 equiv) and NiC12(dppp) (157 mg, 0.29 mmol, 0.03 equiv) in THF (15 mL) is added to the freshly prepared dimethylzinc reagent. The reaction mixture is stirred under for 3h and cooied to room temp. The reaction is quenched carefully with sat’d NH4CI solution and allowed to stir overnight. The layers are separated and the aqueous layer is extracted with EtOAc (2 X 30 mL). The combined organic extracts are washed with brine, dried over Na2Spsi4 and concentrated under reduced pressure to give a cream-colored solid that is used without further purification. MS = 110.08 (M +1). 1H NMR (400 MHz, CDCI3) delta 7.78 (IH, s), 7.72 (IH, s), 4.59 (2H, bs), 2.35 (3H, s).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Amino-6-chloropyrazine, and friends who are interested can also refer to it.

Reference:
Patent; NEUROGEN CORPORATION; WO2008/83070; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 939412-86-9, These common heterocyclic compound, 939412-86-9, name is (3-Chloropyrazin-2-yl)methanamine 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.

(f) (3S,7R,9aS)-N-((3-chloropyrazin-2-yl)methyl)-3-methyl-4-oxooctahydropyrido[2,1-c][1,4]oxazine-7-carboxamide To a solution of (3S,7R,9aS)-3-methyl-4-oxooctahydropyrido[2,1-c][1,4]oxazine-7-carboxylic acid (55 mg, 0.26 mmol) in anhydrous DCM (1 mL) was added oxalyl dichloride (0.068 mL, 0.77 mmol) in DCM (0.5 mL) at 0 C. under N2 atmosphere, and followed by 1 drop of DMF. The resulting mixture was stirred at 0 C. for 2 hrs. The reaction mixture was evaporated, dissolved with DCM (0.5 mL), and added to a solution of (3-chloropyrazin-2-yl)methanamine hydrochloride (56.1 mg, 0.31 mmol), and triethylamine (0.079 mL, 0.57 mmol) in DCM (1 mL), at 0 C. under N2 atmosphere, and the mixture was stirred for 12 hrs at 15 C. Then the mixture was diluted with DCM (5 mL), and H2O (5 mL). The organic layer was washed with brine (5 mL), dried over Na2SO4, evaporated to get the crude product, which was then purified by prep-TLC (PE/THF=1:1) to give (3S,7R,9aS)-N-((3-chloropyrazin-2-yl)methyl)-3-methyl-4-oxooctahydropyrido[2,1-c][1,4]oxazine-7-carboxamide (55 mg, yield: 62.9%). 1H NMR (400 MHz, CDCl3) delta=8.42 (d, J=2.5 Hz, 1H), 8.29 (d, J=2.5 Hz, 1H), 7.17 (br. s., 1H), 4.76-4.57 (m, 2H), 4.16 (q, J=6.9 Hz, 1H), 3.92 (dd, J=4.1, 12.2 Hz, 1H), 3.74 (dd, J=2.5, 12.0 Hz, 1H), 3.37-3.25 (m, 1H), 2.73 (t, J=12.3 Hz, 1H), 2.42 (tt, J=4.0, 11.8 Hz, 1H), 2.18-2.03 (m, 2H), 1.99-1.84 (m, 1H), 1.79-1.68 (m, 2H), 1.44 (d, J=7.0 Hz, 3H).

Statistics shows that (3-Chloropyrazin-2-yl)methanamine hydrochloride is playing an increasingly important role. we look forward to future research findings about 939412-86-9.

Reference:
Patent; KIM, RONALD M.; Liu, Jian; Gao, Xiaolei; Boga, Sobhana Babu; Guiadeen, Deodialsingh; Kozlowski, Joseph A.; Yu, Wensheng; Anand, Rajan; Yu, Younong; Selyutin, Oleg B.; Gao, Ying-Duo; Wu, Hao; Liu, Shilan; Yang, Chundao; Wang, Hongjian; US2014/206681; (2014); 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 50866-30-3 as follows. Recommanded Product: 50866-30-3

To a solution of 6-[(3S,4S)-4-ethylpyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one (4.4 g) in dimethylformamide (62 mL) was added acetic acid (2.4 mL), 5-methylpyrazine-2-carbaldehyde (2 g) and sodium triacetoxyborohydride (5.27 g). The reaction mixture stirred for 2 h at ambient temperature and was carefully quenched with saturated sodium bicarbonate solution, extracted 3* with methylene chloride, dried with magnesium sulfate, filtered and concentrated. Purification via Biotage MPLC chromatography eluding with 1-4% methanolmethylene chloride/0.5% saturated ammonium hydroxide provided the title compound (3.9 g). 400 MHz 1H NMR (CDCl3) delta 8.52-8.48 (m, 1H), 8.38 (s, 1H), 8.02 (s, 1H), 4.81-4.75 (m, 1H), 4.11-4.01 (m, 3H), 3.79-3.75 (m, 1H), 3.60-3.53 (m, 2H), 3.40-3.32 (m, 1H), 3.10-3.08 (m, 1H), 2.94 (m, 1H), 2.63-2.57 (m, 1H), 2.53 (d, J=7.5 Hz, 1H), 2.37-2.18 (m, 4H), 1.90-1.83 (m, 2H), 1.67-1.60 (m, 1H), 1.54-1.47 (m, 1H), 0.95-0.92 (m, 3H). MS: (M+H m/z 424.2).

According to the analysis of related databases, 50866-30-3, the application of this compound in the production field has become more and more popular.

Reference:
Patent; Pfizer Inc; US2009/30003; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Reference of 486424-37-7, These common heterocyclic compound, 486424-37-7, name is 3-Amino-6-bromopyrazine-2-carboxylic acid, 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.

3-Amino-6-bromo -N- (3,4- difluorobenzyl) pyrazine-2-carboxamide: A mixture of 1.51 g 3-amino-6-bromo-2-carboxylic acid (6.93 mM mole), 30 ml dimethylformamide, 1.23 ml 3,4-difluoro benzylamine (10.4 mmol) and 2.40 ml N, N- diisopropylethylamine (13.8 mmol) in combination and stirred together, the batch and then 2.89 g (7-azo BTA) -N, N, N ‘, N’- tetramethyluronium hexafluorophosphate (7.60 mmol) and stirred for two hours , was added 250 ml of ethyl acetate and 150 ml of water, filtered, the organic phase was washed with 150 ml aqueous sodium bicarbonate wash, 50 ml brine, dried over magnesium sulfate drained, purified by flash column chromatography (0-50 % ethyl acetate; n-hexane), to collect 0.899 g of yellow powder (38%).

The synthetic route of 486424-37-7 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BIOGEN MA INC.; SUNESIS PHARMACEUTICALS, INC.; ARNDT, JOSEPH; CHAN, TIMOTHY; GUCKIAN, KEVIN; KUMARAVEL, GNANASAMBANDAM; LEE, WEN-CHERNG; LIN, EDWARD YIN-SHIANG; SCOTT, DANIEL; SUN, LIHONG; THOMAS, JERMAINE; VAN VLOTEN, KURT; WANG, DEPING; ZHANG, LEI; ERLANSON, DANIEL; (469 pag.)TWI525093; (2016); B;,
Pyrazine – Wikipedia,
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. 33332-25-1, name is Methyl 5-chloropyrazine-2-carboxylate, A new synthetic method of this compound is introduced below., name: Methyl 5-chloropyrazine-2-carboxylate

Preparation 10 To a solution of methyl 5-chloropyrazine-2-carboxylate (500 mg) in MeOH (5 mL) was added 28% NH3 aqueous solution (5 mL), and the mixture was stirred at ambient temperature. The precipitated solid was collected by filtration and washed with diisopropyl ether to afford 5-chloropyrazine-2-carboxamide (303 mg) as a solid.

The synthetic route of 33332-25-1 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Astellas Pharma Inc.; EP2123651; (2009); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Some common heterocyclic compound, 939412-86-9, name is (3-Chloropyrazin-2-yl)methanamine hydrochloride, molecular formula is C5H7Cl2N3, 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. Recommanded Product: 939412-86-9

(e) (trans)-benzyl 7-(((3-chloropyrazin-2-yl)methyl)carbamoyl)-4-oxohexahydro-1H-pyrido[1,2-a]pyrazine-2(6H)-carboxylate A mixture of (trans)-2-((benzyloxy)carbonyl)-4-oxooctahydro-1H-pyrido[1,2-a]pyrazine-7-carboxylic acid (1.3 g, 3.9 mmol), (3-chloropyrazin-2-yl)methanamine hydrochloride (840 mg, 4.7 mmol), HATU (2.2 g, 5.8 mmol) and TEA (1.6 g, 15.6 is mmol) in DMF (20 mL) was stirred at 25 C. for overnight. Then the reaction mixture was poured into water and extracted with EA (50 ml*3). The combined organic phase was washed with brine (100 mL), dried over Na2SO4, concentrated under vacuum to give the crude residue, which was purified by silica gel column chromatography (PE/THF=1/3) to give (trans)-benzyl 7-(((3-chloropyrazin-2-yl)methyl)carbamoyl)-4-oxohexahydro-1H-pyrido[1,2-a]pyrazine-2(6H)-carboxylate (600 mg, yield 35.3%). 1H NMR (400 MHz, CD3OD) delta=8.52 (d, J=2.5 Hz, 1H), 8.33 (d, J=2.3 Hz, 1H), 7.40-7.29 (m, 5H), 5.15 (br. s., 2H), 4.77-4.67 (m, 1H), 4.12 (br. s., 1H), 3.96-3.85 (m, 1H), 3.48 (br. s., 2H), 2.71 (t, J=12.5 Hz, 1H), 2.52-2.36 (m, 1H), 2.11-1.97 (m, 2H), 1.90-1.71 (m, 2H).

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 939412-86-9, its application will become more common.

Reference:
Patent; KIM, RONALD M.; Liu, Jian; Gao, Xiaolei; Boga, Sobhana Babu; Guiadeen, Deodialsingh; Kozlowski, Joseph A.; Yu, Wensheng; Anand, Rajan; Yu, Younong; Selyutin, Oleg B.; Gao, Ying-Duo; Wu, Hao; Liu, Shilan; Yang, Chundao; Wang, Hongjian; US2014/206681; (2014); A1;,
Pyrazine – Wikipedia,
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. 17890-77-6, name is 3-Amino-6-bromopyrazine-2-carboxamide, A new synthetic method of this compound is introduced below., Computed Properties of C5H5BrN4O

Step 3: Synthesis of Intermediate D’ as described in the general scheme: 2,5-dibromo-3-amidopyrazine A mixture of C’ (200 g, 922 mM), aq. hydrobromic acid 47% (500 mL) and acetic acid (100 mL) is cooled to -10 C. Bromine (47.25 mL, 922 mM) is then added to the reaction mixture over 45 min at -10 C. A solution of sodium nitrite (190 g, 2.765 M) in water (400 mL) is then added over 2h, whilst maintaining the reaction mixture temperature below -5 C. Upon completion of the addition, the reaction mixture is further stirred for 30 min. A solution of sodium thiosulfate (250 g) in water (712 mL) is then added over 30 min forming a suspension. The solid is isolated by filtration, washed with water (400 mL*2) and dried at 50-55 C. under vacuum to afford crude D’. Crude D’ (186 g) is suspended in a solution of 2-butanone (93 mL) and hexane (279 mL) and then stirred at 30 C. for 1 hr. The solid is isolated by filtration, the cake is washed with a 1:3 mixture of 2-butanone (93 mL) and hexane (186 mL) and dried at 50 C. for 3 hrs to afford clean D’.

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; WIGERINCK, Piet Tom Bert Paul; ANDREWS, Martin James Inglis; De WEER, Marc Maurice Germain; SABOURAULT, Nicholas Luc; KLUGE, Stefan Christian; US2011/118269; (2011); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 14667-55-1, name is 2,3,5-Trimethylpyrazine, 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. Recommanded Product: 2,3,5-Trimethylpyrazine

General procedure: An equimolecular mixture of 2,3-dimethylpyrazine (0.46 mmol, 50 mg) and 3,5-dichlorosalicylic acid (0.46 mmol, 95.8 mg) was dissolved in 15 mL ethanol at room temperature and stirred for about 30 min, followed by filtrating and slow evaporation. Colorless block-like crystals were obtained within 2 weeks with the total yield of 23.3%. IR (KBr pellet, cm-1): 3456, 3084, 2856, 2423, 1669, 1580, 1441, 1358, 1313, 1225, 1169, 1008, 875, 803, 742, 697, 608, 553. The colorlessblock-like crystal of cocrystal 2 and colorless needle crystals of cocrystal 3 were obtained in the similar way as cocrystal 1, but utilized 2,5-DMP and TMP instead of 2,3-DMP, with the total yield of 30.2% and 25.2%, respectively. IR (KBr pellet, cm-1) for cocrystal 2: 3445, 3079, 2868, 2402, 1669, 1586, 1447, 1363, 1308, 1225, 1175, 1053, 880, 803, 753, 692, 608, 558. IR (KBr pellet, cm-1) for cocrystal 3: 3445, 3073, 2935, 2402, 1669, 1586, 1441, 1391, 1352, 1285, 1241, 1175, 1024, 886, 708, 603, 558.

The synthetic route of 2,3,5-Trimethylpyrazine has been constantly updated, and we look forward to future research findings.

Reference:
Article; Zhang, Ya-an; Yan, Cui-Min; Chen, Chen; Zhao, Xiao-Qing; Li, Tian; Sun, Bai-Wang; Research on Chemical Intermediates; vol. 45; 11; (2019); p. 5745 – 5760;,
Pyrazine – Wikipedia,
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. 98-97-5, name is Pyrazine-2-carboxylic acid, A new synthetic method of this compound is introduced below., COA of Formula: C5H4N2O2

General procedure: A catalytic amount of concentrated H2SO4 wasadded to a solution of carboxylic acids 16(a-j) (1.0 mmol)in 50 mL of methanol, and the mixture was refluxed for 6 h. It was allowed to cool. The saturated solution ofNaHCO3 was added to the reaction mixture, and it wasextracted with EtOAc (2 X 50 mL). The combined organiclayer was dried Na2SO4 and concentrated to obtain puremethyl esters 17(a-j).

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:
Article; Murty; Penthala, Raju; Polepalli, Sowjanya; Jain; Medicinal Chemistry Research; vol. 25; 4; (2016); p. 627 – 643;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem