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, 767340-03-4, 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.

Into a flask was charged [Rh(cod)2]OTf (0.1 mmol) and (S) -Cy2-p-Tol-Biphemp (Ligand E) (0.1 mmol) under a nitrogen atmosphere. Degassed trifluoroethanol was then added (20 mL) and the mixture was stirred at room temperature for 1 h. Into a hydrogenator was charged the enamine amide 2-4 (1 mmol) and then degassed. The catalyst solution was then transferred to the hydrogenator under nitrogen. After degassing three times, the enamine amide was hydrogenated under 100 psig hydrogen gas at 20 ¡ãC for 20 h (94percent assay yield, 98percent ee). 1H NMR (300 MHz, CD3CN): No. 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 , 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 following high-performance liquid chromatographic (HPLC) conditions were used to determine percent conversion to product: Column: Waters Symmetry C18, 250 mm x 4.6 mm Eluent: Solvent A: 0.1 vol percent HC104/H20 Solvent B: acetonitrile Gradient: 0 min 75percent A : 25percent B 10 min 25percent A : 75percent B 12.5 min 25percent A: 75percent B 15 min 75percent A : 25percent B Flow rate: 1 mL/min Injection Vol. : 10 muL UV detection: 210 nm Column temp.: 40 ¡ãC Retention times: compound 2-4: 9.1 min compound 2-5: 5.4 min The following high-performance liquid chromatographic (HPLC) conditions were used to determine optical purity: Column: Chirapak, AD-H, 250 mm x 4.6 mm Eluent: Solvent A: 0.2 vol.percent diethylamine in heptane Solvent B: 0.1 vol percent diethylamine in ethanol Isochratic Run Time: 18 min Flow rate: 0.7 mL/min Injection Vol.: 7 muL UV detection: 268 nm Column temp.: 35 ¡ãC Retention times: (R) -amine 2-5: 13.8 min (S)-amine: 11.2 min

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

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 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 H3PO4 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, Jcp= 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.

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 767340-03-4.

Reference:
Patent; MERCK & CO., INC.; WO2005/72530; (2005); A1;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

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 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 H3PO4 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, 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 2-5 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 C and aged 1 h at 40C and then cooled to 25 C over 2 h. (d) Heptane (7L/kg) is charged over 7 h and the slurry stirred for 12 h at 22-25C. 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 C. (g) The optical purity of the free base is about 99% ee.

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 767340-03-4.

Reference:
Patent; MERCK & CO., INC.; WO2005/20920; (2005); A2;,
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem