Tag: M.W=400-500

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, 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. 767340-03-4

Into a 500 ml flask were charged chloro(l,5-cyclooctadiene)rhodium(I) dimer {[Rh(cod)Cl]2}(292 mg, 1.18 mmol) and (R,S) f-butyl Josiphos (708 mg, 1.3 mmol) under a nitrogen atmosphere. Degassed MeOH was then added (200 mL) and the mixture was stirred at room temperature for 1 h. Into a 4 L hydrogenator was charged the enamine amide 2Lambda (118 g, 0.29 mol) along with MeOH (1 L). The slurry was degassed. The catalyst solution was then transferred to the hydrogenator under nitrogen. After degassing three times, the enamine amide was hydrogenated under 200 psi hydrogen gas at 50 0C for 13 h. Assay yield was determined by EtaPLC to be 93% and optical purity to be 94% ee.The optical purity was further enhanced in the following manner. The methanol solution from the hydrogenation reaction (18 g in 180 mL MeOH) was concentrated and switched to methyl t- butyl ether (MTBE) (45 mL). Into this solution was added aqueous Eta3PO4 solution (0.5 M, 95 mL).After separation of the layers, 3NNaOH (35 mL) was added to the water layer, which was then extracted with MTBE (180 mL + 100 mL). The MTBE solution was concentrated and solvent switched to hot toluene (180 mL, about 75 0C). The hot toluene solution was then allowed to cool to 0 0C slowly (5 – 10 h). The crystals were isolated by filtration (13 g, yield 72%, 98 – 99% ee); m.p. 114.1 – 115.7 0C. lH NMR (300 MHz, CD3CN): delta 7.26 (m), 7.08 (m), 4.90 (s), 4.89 (s), 4.14 (m), 3.95 (m), 3.40 (m), 2.68(m), 2.49 (m), 1.40 (bs).Compound 2-5 exists as amide bond rotamers. Unless indicated, the major and minor rotamers are grouped together since the carbon-13 signals are not well resolved: 13c NMR (CD3CN): delta 171.8, 157.4 (ddd , JCF = 242.4, 9.2, 2.5 Hz), 152.2 (major), 151.8 (minor), 149.3(ddd; JCF = 246.7, 14.2, 12.9 Hz), 147.4 (ddd, JCF = 241.2, 12.3, 3.7 Hz), 144.2 (q, JCF = 38.8 Hz), 124.6 (ddd , JCF = 18.5, 5.9, 4.0 Hz), 120.4 (dd , JCF = 19.1, 6.2 Hz), 119.8 (q, JCF = 268.9 Hz), 106.2 (dd , JCF = 29.5, 20.9 Hz), 50.1, 44.8, 44.3 (minor), 43.2 (minor), 42.4, 41.6 (minor), 41.4, 39.6, 38.5 (minor), 36.9. The crystalline free base 2^ can also be isolated as follows:(a) The reaction mixture upon completion of the hydrogenation step is charged with 25 wt% of Ecosorb C-941. The mixture is stirred under nitrogen for one h and then filtered. The cake is washed with 2L/kg of methanol. Recovery of free base is about 95% and optical purity about 95% ee.(b) The freebase solution in methanol is concentrated to 3.5-4.0 L/kg volume (based on free base charge) and then solvent-switched into isopropanol (IPA) to final volume of 3.0 L/kg IPA.(c) The slurry is heated to 40 0C and aged 1 h at 4O0C and then cooled to 25 0C over 2 h. EPO (d) Heptane (7L/kg) is charged over 7 h and the slurry stirred for 12 h at 22-250C. The supernatant concentration before filtering is 10-12 mg/g.(e) The slurry is filtered and the solid washed with 30% IPA/heptane (2L/kg).(f) The solid is dried in a vacuum oven at 40 0C. (g) The optical purity of the free base is about 99% ee.

Statistics shows that 767340-03-4 is playing an increasingly important role. we look forward to future research findings about (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.

Reference:
Patent; MERCK & CO., INC.; WO2006/33848; (2006); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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, 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: (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

To 30 ml of degassed triflouroethanol (TFE) were added Ruthenium(II) chloride 1,5-cyclooctadiene complex (18.2 mg, 0.037 mmol) and (R )-(-)-H(S)-2- Diphenylphosphino)ferrocenyl]ethyl di-tert-butylphosphine (44.8 mg, 0.083 mmol). The solution was degassed again, and left to stir at room temperature for 1 hour. To 250 ml glass reactor were added (Z)-3-amino-l-(3-(trifluoromethyl)-5,6-dihydro- [l,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)but-2-en-l-one (30 g, 74.07 mmol) and 100 ml TFE. The slurry was stirred and washed three times with N2. Than, the catalyst solution was added and the mixture washed three times with N2, then switched to H2 and washed three times. The H2 pressure was set to constant pressure of 5 bar and the reaction was heated to 55C for 23 hours. The TFE solution (93.3% purity and 77% R) was evaporated to yield oily-STG-base.

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

Reference:
Patent; TEVA PHARMACEUTICAL INDUSTRIES LTD.; TEVA PHARMACEUTICALS USA, INC.; WO2009/70314; (2009); 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

Synthetic Route of 767340-03-4, A 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, 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.

(Z)-3-amino-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]-pyrazyn-7(8H)-yl)-4-(2,4,5-trifluorophenyl)but-2-en-1-one (10 gr, 1 equivalent) and methanol (50 ml) were added to a 250 ml hydrogenation bottle at 25 C. and the bottle was subjected to vacuum and nitrogen backflush three times. The catalyst solution was added to the hydrogenation bottle and the bottle was again subjected to vacuum and nitrogen backflush three times and then to vacuum and backflush with hydrogen gas three times. The resulting reaction mixture was maintained under hydrogen at a pressure of 5 bar and heated to 55 C. The heated mixture was stirred at 5 bar pressure, at 55 C. for 3 days to obtain Sitagliptin base in methanol solution (optical purity by HPLC 97%, purity by HPLC 63.7%).

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

Reference:
Patent; Teva Pharmaceutical Industries Ltd.; US2010/249140; (2010); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

These 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, 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. category: Pyrazines

Ligand Metal precursor percentyieldb percent eec config. 15 3 A [Rh(cod) 2]BF4 77 88 R 4 B [Rh(cod)Cl]2 58 76 R 5 C [Rh(cod)Cl]2 15 78 a: Reaction conditions: in TFE, 5 molpercent metal precursor, 5 molpercent ligand, 90 psig H2, 50 °C, 18 h; b: Assayed by HPLC; c: Assayed by chiral HPLC using a AS-RH chiral column eluting with 20percent acetonitrile/water as the mobile phase.

The synthetic route of (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 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; MERCK & CO., INC.; SOLVIAS AG; WO2005/97733; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 767340-03-4, These 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, 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.

Into a flask were charged bis(norbomadiene)rhodium(I) tetrafluoroborate {[Rh(nbd) 2]BF4}(41.55 mg, 0.1 mmol), Ligand D (69.73 mg, 0.1 mmol) and the enamine amide 2-4 (45 g, 111.1 mmol) under a nitrogen atmosphere. To this mixture a solvent mixture of 37.5 mL methanol (extra dry and degassed) and 112.5 mL 2,2,2-trifluoroethanol (distilled and degassed) were added. The slurry was then transferred under nitrogen into an stainless steel autoclave and sealed. The autoclave was then heated to 50 C and pressurized to 500 psig with hydrogen. A sample taken after 17 hours was analyzed using HPLC, which confirmed the end of the reaction giving 94% assay yield and 94% ee.

Statistics shows that (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 is playing an increasingly important role. we look forward to future research findings about 767340-03-4.

Reference:
Patent; MERCK & CO., INC.; SOLVIAS AG; WO2005/97733; (2005); 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. 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, A new synthetic method of this compound is introduced below., Recommanded Product: (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

Example-26: Preparation of racemic sitagliptin compound of formula-18:; Sodium borohydride (2.34 grams) was added to a mixture of compound of formula-17 (25 grams) in toluene at 5-100C. Acetic acid (75 ml) was added to it and stirred for 3 hours. The reaction mixture was quenched with water and then layers were separated. The aqueous layer was basified with aqueous sodium hydroxide and then the reaction mixture extracted into methylene chloride. The extracted methylene chloride dried over sodium sulphate and then solvent from it distilled off completely to get the title compound. Yield: 24 grams

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; MSN LABORATORIES LIMITED; SATYANARAYANA REDDY, Manne; ESWARAIAH, Sajja; SATYANARAYANA, Revu; KONDAL REDDY, Bairy; SRINIVAS, Aluru; WO2010/122578; (2010); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Application of 767340-03-4, A 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, 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.

Into a 500 ml flask were charged chloro(l,5-cyclooctadiene)rhodium(l) dimer {[Rh(cod)CI]2} (292 mg, 1.18 mmol) and (R,S) t-butyl Josiphos (708 mg, 1.3 mmal) under a nitrogen atmosphere. Degassed MeOH was then added (200 ml_) and the mixture was stirred at room temperature for 1 h. Into a 4L hydrogenator was charged the enamine amide (VII) (118 g, 0.29 mal), MeOH (1 L). The catalyst solution was then transferred to the hydrogenator. After degassing three times, the enamine amide was hydrogenated under 200 psi hydrogen at 50 C for 13 h. The obtained methanol solution was concentrated and switched to methyl t-butyl ether (MTBE) (45 ml_). Into this solution was added aqueous H3P04 solution (0.5 M, 95 ml_). After separation of the layers, 3N NaOH (35 ml_) was added to the water layer, which was then extracted with MTBE (180 ml_ + 100 ml_). The MTBE solution was concentrated and solvent switched to hot toluene (180 ml_, about 75 C). The toluene solution was then cooled to O C. The crystals were isolated by filtration to obtained Sitagliptin (I) (13 g, yield 72%, 98-99% ee);

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

Reference:
Patent; F.I.S. – FABBRICA ITALIANA SINTETICI S.P.A.; SHI, Terry; LOU, Sam; DE LUCCHI, Ottorino; PADOVAN, Pierluigi; (45 pag.)WO2019/158285; (2019); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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. 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 belongs to pyrazines compound, it is a common compound, a new synthetic route is introduced below. Product Details of 767340-03-4

Into a 500 ML flask were charged chloro (1, 5-cyclooctadiene) rhodium (I) dimer { [Rh (cod) Cl] 2} (292 mg, 1.18 mmol) and (R, S) t-butyl Josiphos (708 mg, 1.3 mmol) under a nitrogen atmosphere. Degassed MEOH was then added (200 mL) and the mixture was stirred at room temperature for 1 h. Into a 4 L hydrogenator was charged the enamine amide 2-4 (118 g, 0.29 mol) along with MEOH (1 L). The slurry was degassed. The catalyst solution was then transferred to the hydrogenator under nitrogen. After degassing three times, the enamine amide was hydrogenated under 200 psi hydrogen gas at 50 C for 13 h. Assay yield was determined by HPLC to be 93% and optical purity to be 94% ee. The optical purity was further enhanced in the following manner. The methanol solution from the hydrogenation reaction (18 g in 180 mL MEOH) was concentrated and switched to methyl t- butyl ether (MTBE) (45 mL). Into this solution was added aqueous H3P04 solution (0.5 M, 95 mL). After separation of the layers, 3N NAOH (35 mL) was added to the water layer, which was then extracted with MTBE (180 ML + 100 mL). The MTBE solution was concentrated and solvent switched to hot toluene (180 ML, about 75 C). The hot toluene solution was then allowed to cool to 0 C slowly (5-10 h). The crystals were isolated by filtration (13 g, yield 72%, 98-99% ee); m. p. 114. 1-115. 7 C. 1H NMR (300 MHz, CD3CN) : 8 7.26 (m), 7. 08 (m), 4.90 (s), 4.89 (s), 4.14 (m), 3.95 (m), 3.40 (m), 2.68 (m), 2.49 (m), 1.40 (bs). Compound 2-5 exists as amide bond rotamers. Unless indicated, the major and minor rotamers are grouped together since the carbon-13 signals are not well resolved: 13C NMR (CD3CN) : 8 171.8, 157.4 (ddd, JCF = 242.4, 9.2, 2.5 Hz), 152.2 (major), 151.8 (minor), 149.3 (ddd; JCF = 246.7, 14.2, 12.9 Hz), 147.4 (ddd, JCF = 241. 2,12. 3,3. 7 Hz), 144.2 (q, JCF = 38. 8 HZ), 124.6 (ddd, 7CL= 18.5, 5.9, 4.0 Hz), 120.4 (dd, JCF = 19.1, 6.2 HZ), 119.8 (q, JCF = 268.9 Hz), 106.2 (dd, JCF = 29.5, 20.9 Hz), 50.1, 44. 8, 44.3 (minor), 43.2 (minor), 42.4, 41.6 (minor), 41.4, 39.6, 38. 5 (minor), 36.9.

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

Reference:
Patent; MERCK & CO., INC.; WO2005/30127; (2005); A2;,
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. 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, A new synthetic method of this compound is introduced below., COA of Formula: C16H13F6N5O

Example 2: (0128) Preparation of (R)-3-amino-l-(3-(trifluoromethyl)-5,6-dihvdro-ri,2,41triazolor4,3-alpyrazin- 7(8H)-yl)-4-(2A5-trifluorophenyl)butan-l-one (S)-3-(2-amino-2-oxoethyl)-5-methyl hexanoate (Sitagliptin diastereomeric salt). (0129) Mixture of (Z)-3-amino-l-(3-(trifluoromethyl)-5,6-dihydro-[l,2,4]triazolo[4,3-a]pyrazin- 7(8H)-yl)-4-(2,4,5-trifluorophenyl)but-2-en-l-one (100. Og) and Monochlorobenzene (750.0ml) was cooled to 0-5°C. Sodium borohydride (24.4g; 2.66eq) followed by formic acid (330.0ml; 35.5eq) was added to the reaction mass at 0-5°C and maintained the reaction mass until the completion of the reaction i.e, until the TLC complies at the same temperature. Water (1600.0ml) was added after TLC complies and raised the temperature of the reaction mass to 50-55°C. Separated the aqueous & organic layers and washed the aqueous layer with Monochlorobenzene (200ml). To the aqueous layer Methelenedichloride (300ml) was added and adjusted the pH of the reaction mass to 10-11 with 48percent caustic lye. Separated the aqueous & organic layers and extracted the aqueous layer with Methelenedichloride (MDC). Combined all the organic layers and washed with 20percent sodium chloride solution, followed by water. Distilled off the Organic layer and co-distilled with isopropyl alcohol (100.0ml). To the obtained racemic Sitagliptin crude was added isopropyl alcohol (500.0ml) and (S)-3-(2- amino-2-oxoethyl)-5-methylhexanoicacid (28.0g), heated the mixture to reflux and slowly cooled to room temperature. Filtered the precipitated solid and washed with Isopropyl alcohol (100.0ml). To the wet cake isopropyl alcohol (200.0ml) was added and heated to reflux. Cooled the reaction mixture to room temperature filtered the product and washed with isopropyl alcohol (75.0ml). The wet cake was dried under vacuum at 50-55°C to obtain 57. Og of Sitagliptin diastereomeric salt. Molar yield: 38.7percent; Chiral HPLC: Desired product: 99.78percent; Isomer: 0.22percent, Purity by HPLC >99.0percent; SOR:-20.0°; Melting range: 168-172°C.

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; LEE PHARMA LIMITED; ALLA, Venkat Reddy; ALLA, Raghumitra; MALLEPALLI, Srinivas Reddy; NANDAM, Suresh Babu; GUDA, Madhukar Reddy; ALLURI, Raja Reddy; (33 pag.)WO2016/110750; (2016); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem