The synthetic route of 7,7-Dimethyl-2,3,4,6,7,8-hexahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-one has been constantly updated, and we look forward to future research findings.
Related Products of 1346674-23-4, 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. 1346674-23-4, name is 7,7-Dimethyl-2,3,4,6,7,8-hexahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-one belongs to amides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.
0298] Example 10B (0458) [0299] Compound 170 was prepared from compounds 160 and 100 as follows: (0459) (0460) [0300] Potassium carbonate (20.3 g, 1.5 eq., 147 mmol), compound 100 (19 g, 1.1 eq., 108 mmol), compound 160 (20 g, 1 eq., 97.9 mmol), DPPF ligand (2.2 g, 0.04 eq., 3.9 mmol), and Pd(OAc)2 catalyst (0.44 g, 0.02 eq., 2 mmol) were charged to a reactor. THF (200 mL, 10 mL/g) was charged to the reactor with agitation. The reactor was evacuated and filled with N2 three times and the contents were then heated to 68C with reflux. The reactor was sampled at 22 hours and the compound 160 content was 0.9 area% by HPLC. The reactor contents were cooled to 65C and water (200 mL, 10 mL/g) was charged to the reactor over 4 hours and the reactors contents were then held at 20C for a minimum of 3 hours. The reactor contents were filtered and compound 170 was collected as a solid. The solid compound 170 was rinsed with THF/water (1 : 1 mixture, 200 mL, 10 mL/g). The washed solids were dried under vacuum with N2 purge at 22 C for a minimum of 3 hours. A yield of 84% was obtained with 99 area% by HPLC (245 nm), 79 ppm Pd and 0.2% residue on ignition (“ROI”). Of the impurities, 0.51 A% regioisomer and 0.33%> bis-coupling product were found: (0461) (0462) Regioisomer Bis-Coupling Impurity (0463) [0301] The method was repeated on a 40 g scale (based on compound 160). The coupling reaction was performed using compound 100 (1.1 eq.), Pd(OAc)2 (0.02 eq.), dppf in THF (0.04 eq., 10 mL/g) at 68 C for 28 h to reach 98.4% conversion. Water was added (350 mL) to the reaction mixture over 3 h and aged at 65 C for 10 h, cooled to 20 C in 1.5 h and aged for 16 h. After filtration and drying, a beige solid compound 170 was obtained (57.2 g, 85%, 98.6A%, 0.55A% regioisomer, 0.48A% bis-coupling impurity, 87 ppm Pd and 0.3% ROI). (0464) [0302] The method was repeated on a 609 g scale (based on compound 160). (0465) Potassium carbonate (0.6114 kg, 1.5 eq., 4.34 mol), compound 100 (0.7769 kg, 1.5 eq., 4.41 mol), compound 160 (0.6099 kg, 1 eq., 2.99 mol), DPPF ligand (0.0662 kg, 0.04 eq., 0.119 mmol), and Pd(OAc)2 catalyst (0.0137 kg, 0.02 eq., 0.061 mmol) were charged to an isolator. A reactor was evacuated and filled with N2 three times and charged with the contents of the isolator. THF (10.35 kg, 20 L/kg) was charged to the reactor with agitation. The reactor contents were heated to 68C with reflux. The reactor was sampled at 40 hours and the compound 160 content was 0.3 area% by HPLC. The reactor contents were cooled to 65C and water (6.01 kg, 10 L/kg) was charged to the reactor over 3 hours and the reactor contents were then held at 20C for a minimum of 3 hours. The reactor contents were filtered and compound 170 was collected as a solid. The solid compound 170 was rinsed with THF/water (1 : 1 mixture, 6 L, 10 mL/g). The washed solids were dried under vacuum with N2 purge at 22C for a minimum of 10 hours. A 84% yield (0.8576 kg) was obtained with 99.2 A% by HPLC (245 nm), 24 ppm Pd and less than 0.1% ROI.
The synthetic route of 7,7-Dimethyl-2,3,4,6,7,8-hexahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-one has been constantly updated, and we look forward to future research findings.
Reference:
Patent; F. HOFFMANN-LA ROCHE AG; GENENTECH, INC.; BEAUDRY, Danial; CRAVILLION, Theresa; GOSSELIN, Francis; LIM, Ngiap-Kie; MALHOTRA, Sushant; TIAN, Qingping; ZHANG, Haiming; GMEHLING, Alexander; FETTES, Alec; BACHMANN, Stephan; (130 pag.)WO2018/109050; (2018); A1;,
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