Tag: M.W=100-200

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.

Preparation c-120 5-Bromo-pyrazin-2-ol Sodium nitrite (1,35 g, 19.53 mmol) was added portionwise to concentrated sulfuric acid (9.8 mL) at 0 C. The mixture was heated at 50 C. until all of the sodium nitrite had dissolved and the mixture was again cooled to 0 C. A solution of 5-bromo-pyrazin-2-ylamine (2.57 g, 14.68 mmol) in concentrated sulfuric acid (14.7 mL) was added dropwise to the nitronium solution at 0 C. The ice bath was removed, the mixture warmed to ambient temperature and stirred for 15 minutes before heating to 45 C. for seven minutes. After cooling to ambient temperature, the mixture was poured slowly with precaution into crushed ice water (100 mL). The aqueous phase was neutralized to pH 4 with 20% aqueous sodium hydroxide then extracted with ethyl acetate (3*100 mL). The combined organic extracts were washed with water (50 mL), dried (anhydrous magnesium sulfate), filtered, and evaporated to afford the title compound (1.88 g, 73%) as a yellow solid. 1H NMR (CDCl3, 300 MHz): delta 8.07 (1H, s), 7.62 (1H, d, J=3.0 Hz).

Statistics shows that 2-Amino-5-bromopyrazine is playing an increasingly important role. we look forward to future research findings about 59489-71-3.

Reference:
Patent; Pfizer Inc; US2005/187266; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 1209459-10-8, The chemical industry reduces the impact on the environment during synthesis 1209459-10-8, name is 2-Bromo-5-fluoropyrazine, I believe this compound will play a more active role in future production and life.

Step 2: 2-(4-cyclopropyl-1H-imidazol-1-yl)-9-(5-fluoropyrazin-2-yl)-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-one A suspension of 2-(4-cyclopropyl-1H-imidazol-1-yl)-9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-one (100 mg, 0.225 mmol), 2-bromo-5-fluoropyrazine (90 mg, 0.51 mmol) and Pd(PPh3)4 (39 mg, 0.034 mmol) in DME (2.8 mL) was treated with a 2M aq. solution of Na2CO3 (0.6 mL, 1.12 mmol). The mixture was heated to 90 C. for 2 h, allowed to cool to RT and poured onto H2O. The mixture was extracted with DCM and the combined org. layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash-column chromatography over silicagel (Biotage Isolera Four, eluent: 25% EtOAc in heptane for 2 min, then from 25% EtOAc in heptane to 100% EtOAc in heptane in 10 min, 100% EtOAc in heptane for 5 min) to yield a solid which was crystallized from diethyl ether and afforded the title compound (57 mg). UPLC-MS: MS 415.2 (M-FH+); UPLC rt 0.92 min. 1H NMR (400 MHz, DMSO-d6) delta ppm 0.59-0.69 (m, 2H), 0.72-0.82 (m, 2H), 1.75-1.86 (m, 1H), 2.97 (t, J=5.62 Hz, 2H), 3.70 (t, J=6.11 Hz, 2H), 4.24 (br. s., 2H), 7.15 (s, 1H), 7.43 (s, 1H), 7.54 (t, J=7.82 Hz, 1H), 7.69 (d, J=7.58 Hz, 1H), 8.01-8.16 (m, 2H), 8.58 (s, 1H), 8.83 (d, J=8.31 Hz, 1H). Following the procedure described above for Example 139 and substituting the appropriate reagents, starting materials and purification methods known to those skilled in the art, the following compounds of the present invention were prepared:

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-Bromo-5-fluoropyrazine, other downstream synthetic routes, hurry up and to see.

Reference:
Patent; NOVARTIS AG; BEHNKE, Dirk; CARCACHE, David; ERTL, Peter; KOLLER, Manuel; ORAIN, David; US2014/57902; (2014); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 108-50-9, These common heterocyclic compound, 108-50-9, name is 2,6-Dimethylpyrazine, 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 II Preparation Of 1,2-Bis(6-methyl-2pyrazyl)ethane STR10 The reaction of 5.40 grams (0.05 mole) of 2,6-dimethylpyrazine with 0.05 mole of lithium diisopropylamide and 6.35 grams (0.025 mole) of iodine was carried out as described in Method A of Example I. A crude product was obtained as previously described and the dimeric pyrazine was purified by elution chromatography to yield 1.9 grams (36%) of pure material. Recrystallization from hexane gave plates, m.p. 99-101 C.

Statistics shows that 2,6-Dimethylpyrazine is playing an increasingly important role. we look forward to future research findings about 108-50-9.

Reference:
Patent; Philip Morris Incorporated; US4620004; (1986); A;,
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. 36070-80-1, name is 5-Chloropyrazine-2-carboxylic acid, A new synthetic method of this compound is introduced below., Recommanded Product: 5-Chloropyrazine-2-carboxylic acid

Step 1: 5-chloro-N-[(lS)-l-cyclopropyl-2,2,2-trifluoroethyl]pyrazine-2-carboxamide N,N-Diisopropylethylamine (1.3 mL, 7.5 mmol) was added to a mixture of 5- chloropyrazine-2-carboxylic acid (0.40 g, 2.5 mmol), N,N,N’,N’-tetramethyl-0-(7- azabenzotriazol-l-yl)uronium hexafluorophosphate (1.0 g, 2.8 mmol) and (lS)-l- cyclopropyl-2,2,2-trifluoroethanamine hydrochloride (0.44 g, 2.5 mmol) (ASIBA Pharmatech, Cat.No.: 70092-HCl) in methylene chloride (10 mL). The reaction mixture was stirred at room temperature overnight. The mixture was worked up with saturated aqueous NaHC03, and extracted with ethyl acetate (3x 20 mL). The combined organic layers were washed with brine, dried over MgSC , filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-20%) to afford the desired product (0.51 g, 72%). LCMS (M+H) +: m/z = 280.0/282.0.

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; INCYTE CORPORATION; YAO, Wenqing; BURNS, David M.; ZHUO, Jincong; WO2012/177606; (2012); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Related Products of 4858-85-9,Some common heterocyclic compound, 4858-85-9, name is 2,3-Dichloropyrazine, molecular formula is C4H2Cl2N2, 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.

Preparation 8: 3′-(4-Chloro-phenyl)-3,4,5,6-tetrahydro-2H-[l,2′]bipyrazineCouple 2,3-dichloropyrazine (0.302 g, 2.03 mmol) and 4-chlorophenylboronic acid (0.320 g, 2.05 mmol), using tetrakis(triphenylphosphine)palladium(0) (0.124 g,0.107 mmol), and potassium fluoride (0.355 g, 6.11 mmol) in toluene (19 mL) and water (5 mL), at 100 0C for 17.5 hr. Cool the reaction, partition the layers and extract the aqueous layer with ethyl acetate. Wash the combined organic layers with saturated aqueous sodium chloride, dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with 0: 100 to 35:65 ethyl acetate:hexanes), to give 2-chloro-3- (4-chlorophenyl)-pyrazine (0.199 g, 44%).Couple 2-chloro-3-(4-chlorophenyl)-pyrazine (0.148 g, 0.710 mmol) and piperazine-1-carboxylic acid t-butyl ester (0.216 g, 1.16 mmol), using 2- (dicyclohexylphosphino)biphenyl (0.0321 g, 0.0916 mmol), tris(dibenzylideneacetone) dipalladium (0.0328 g, 0.0388 mmol), and the sodium salt of 2-methylpropan-2-ol (0.104 g, 1.09 mmol) in toluene (9 mL) at 82 0C for 17 hr. Cool the reaction to room temperature, dilute with diethyl ether (50 mL), filter through a 1 cm pad of silica gel, rinse the pad with diethyl ether (2 x 25 mL), combine the organic solutions, concentrate and purify (silica gel chromatography, eluting with 0: 100 to 1 : 1 ethyl acetate:hexanes) to give 3′-(4-chloro-phenyl)-2,3,5,6-tetrahydro-[l,2′]bipyrazinyl-4-carboxylic acid t-butyl ester (0.143 g, 56%). MS (ES): m/z = 303 [M+H-isobutylene]+.Dissolve 3′-(4-chloro-phenyl)-2,3,5,6-tetrahydro-[l,2′]bipyrazinyl-4-carboxylic acid t-butyl ester in DCM (10 mL), add 4 M aqueous HCl (5 equiv) and stir for 2 hr. at ambient temperature. Concentrate under reduced pressure, dissolve in methanol (2 mL) and purify by SCX, eluting the product from the ion-exchange resin using 2 M NH3 in methanol, to give the title preparation (0.103 g, 100%). MS (ES): m/z = 259 [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 2,3-Dichloropyrazine, its application will become more common.

Reference:
Patent; ELI LILLY AND COMPANY; WO2008/141020; (2008); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These common heterocyclic compound, 89283-32-9, name is (3-Chloropyrazin-2-yl)methanol, 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: C5H5ClN2O

Step 2 To a mixture of (3-chloropyrazin-2-yl)methanol (200 mg, 1.4 mmol, 1 eq.), 1-isopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (393 mg, 1.67 mmol, 1.2 eq.), Pd(dppf)Cl2 (102 mg, 0.14 mmol, 0.1 eq.), and K2CO3 (580 mg, 4.2 mmol, 3 eq.) in a RB flask were added dioxane (6 mL) and water (2 mL). The mixture was heated at 100 C. for 1 h, cooled to rt, filtered, concentrated, and purified on silica gel using a mixture of EtOAc and hexanes as eluent to give (3-(1-isopropyl-1H-pyrazol-5-yl)pyrazin-2-yl)methanol (110 mg, 36%) as a yellow oil. LRMS (M+H+) m/z 219.1.

The synthetic route of (3-Chloropyrazin-2-yl)methanol has been constantly updated, and we look forward to future research findings.

Reference:
Patent; Global Blood Therapeutics, Inc.; The Regents of the University of Califorina; Cytokinetics, Inc.; Metcalf, Brian; Chuang, Chihyuan; Warrington, Jeffrey; Paulvannan, Kumar; Jacobson, Matthew P.; Hua, Lan; Morgan, Bradley; US2015/344483; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

27398-39-6, name is 3-Chloropyrazine-2-carboxylic acid, 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. Application In Synthesis of 3-Chloropyrazine-2-carboxylic acid

To a solution of 3-chloropyrazine-2-carboxylic acid (100 mg, 0.63 mmol) in DCM/MeOH (2 mL : 0.2 mL) was added TMSCHN2 (0.47 mL, 0.95 mmol) at RT and the resulting mixture stirred at RT for 2 h. Acetic acid (0.2 mL) was added and the mixture diluted with water (2 mL) and extracted with DCM (4 mL x 3). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo to give the title compound as a oil. LRMS m/z (M+H) 173.0 found, 173.0 required.

The synthetic route of 27398-39-6 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK SHARP & DOHME CORP.; KUDUK, Scott, D.; LIVERTON, Nigel; LUO, Yunfu; (68 pag.)WO2016/89721; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 109838-85-9, 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. 109838-85-9, name is (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine, This compound has unique chemical properties. The synthetic route is as follows.

To a 100 ml three neck round bottomed flask under nitrogen atmosphere, (R)-2- isopropyl-3,6-dimethoxy-2,5-dihydropyrazine (4 g, 21.7 mmol) was dissolved in dry THF (28 ml) and cooled to -78 C. To this reaction mixture, 1 .6 M solution of n-BuLi in hexanes (16.3 ml, 26 mmol) was added dropwise at -78 C and stirred for 15 minutes. A solution of l-bromo-3- (2-bromoethyl)benzene (5.73 g, 21 .7 mmol) in dry THF (13 ml) was added dropwise at -78 C and stirred for 1 h followed by stirring at rt for 3 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted using ethyl acetate. The combined organic layer was dried over sodium sulfate and concentrated and purified by flash column purification with 1 -3 % ethyl acetate in hexanes to yield 3.3 g of (2S,5R)-2-(3-bromophenethyl)-5-isopropyl- 3,6-dimethoxy-2,5-dihydropyrazine.

The chemical industry reduces the impact on the environment during synthesis (R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine. I believe this compound will play a more active role in future production and life.

Reference:
Patent; BRAMELD Kenneth; OWENS Timothy; WO2015/195950; A1; (2015);,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthetic Route of 17231-51-5, 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. 17231-51-5, name is 3-Amino-6-bromopyrazine-2-carbonitrile, This compound has unique chemical properties. The synthetic route is as follows.

Step 1: 3-Amino-6-bromo-N?-hydroxypyrazine-2-carboximidam ide To a 20m1 flask was added 3-amino-6-bromopyrazine-2-carbonitrile (600 mg, 3.01 mmol) inMeOH (12 ml) and cooled to 000. To the reaction mixture was added hydroxylaminehydrochloride (210 mg, 3.01 mmol) and triethylamine (0.420 ml, 3.01 mmol) and the mixturewas allowed to warm to room temperature as a precipitate formed. The precipitate was filtered off and washed with MeOH. The filtrate was concentrated under reduced pressure and the resulting solid triturated in MeOH to give a second crop of product. The solid was triturated in MeOH again and sonicated for l5mins until a suspension formed. The solid wasfiltered off and dried in a vacuum oven at 40C for 3 hours to afford the title compound;1H NMR (400MHz, DMSO-d6), O 10.38 (1H, 5), 8.15 (1H, 5), 7.64 (2H, brs), 5.88 (2H, 5).

The chemical industry reduces the impact on the environment during synthesis 3-Amino-6-bromopyrazine-2-carbonitrile. I believe this compound will play a more active role in future production and life.

Reference:
Patent; NOVARTIS AG; BELLENIE, Benjamin Richard; BLOOMFIELD, Graham Charles; BRUCE, Ian; CULSHAW, Andrew James; HALL, Edward Charles; HOLLINGWORTH, Gregory; NEEF, James; SPENDIFF, Matthew; WATSON, Simon James; (395 pag.)WO2015/162459; (2015); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Electric Literature of 19847-12-2,Some common heterocyclic compound, 19847-12-2, name is Pyrazinecarbonitrile, molecular formula is C5H3N3, 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: 2-Cyanopyridine (0.420 ml; 4 mmol) was dissolved in absolute methanol (20 ml) and to it was added sodium methoxide solution in methanol (1.0 ml) (previously prepared). The reaction contents were stirred at room temperature for 2 h 1,4-diaminobutane (0.18 ml, 2 mmol) was added to the reaction mixture. Reaction contents were heated under reflux for 12 h. Solvent was removed under reduced pressure. Crude product so obtained was washed with diethyl ether and then with ethyl acetate to give thick mass. Solvent traces from this thick mass was removed by applying high vacuum for 15 min to give semisolid product i.e. N-(2-pyridineimidoylamino-butyl)-pyridine-2-carboxamidine (5a). Yield 480 mg (81%).

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

Reference:
Article; Arya, Surbhi; Kumar, Nikhil; Roy, Partha; Sondhi; European Journal of Medicinal Chemistry; vol. 59; (2013); p. 7 – 14;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem