With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.1059630-08-8,(4aS,9bR)-Ethyl 6-bromo-3,4,4a,5-tetrahydro-1H-pyrido[4,3-b]indole-2(9bH)-carboxylate,as a common compound, the synthetic route is as follows.
Example 5-A: Production of (6bR,10aS)-ethyI 2,3,6b,9,10,10a-hexahydro-2-oxo-lH- pyrido [3 ‘,4’ :4,5]-py rrolo [1 ,2,3-de] quinoxaline-8-carboxy late; Alternative to Example 5 above, (6bR, 1 OaS)-ethyl 3,6b,9, 10, 1 Oa- hexahydro-3 -methyl-2-oxo- 1 H-pyrido [3 ‘ ,4 ‘ :4,5]-pyrrolo [ 1 ,2,3 -de]quinoxaline-8- carboxylate may also be made in a one pot method starting from Compound of Formula ID. A 2 liter 4 neck round bottom flask is equipped with a mechanical stirrer, reflux condenser, N2 inlet, teflon covered K-type temperature probe with a controller, and a heating mantle. To the flask is charged (4aS,9bR)-ethyl 6-bromo-3,4,4a,5-tetrahydro- lH-pyrido[4,3-b]indole-2(9bH)-carboxylate (250 g, 769 mmol), chloroacetamide (124 g, 1153 mmol, 1.5 equiv), potassium iodide (191.5 g, 1160 mmol, 1.5 equiv), diisopropyl ethylamine (266 mL, 1531 mmol, 2.0 equiv), and dioxane (625 mL). The reaction is heated to reflux temperature of about 103 0C until less than 3% of the starting substrate is observed by HPLC (about 48 hours). Additional charge of N- methyl chloroacetamide and diisopropyl ethylamine maybe necessary. The reaction is then cooled to ca. 80 0C, and at this temperature copper iodide (29.2 g, 153.8 mmol, 0.2 equiv), potassium carbonate (232.5 g, 1682 mmol, 2.2 equiv), dimethylethylene diamine (49.6 mL, 461 mmol, 0.6 equiv), and additional dioxane (375 mL) is added. The reaction is then re-heated to reflux and is monitored by HPLC. Reflux occurs at ca. 103 0C. The reaction is monitored by HPLC.; Example 6-A: Production of (6bR,10aS)-ethyl 2,3,6b,9,10,10a-hexahydro-3-methyl- 2-oxo-lH-pyrido[3%4′:4,5]-pyrrolo[l,2,3-de]quinoxaline-8-carboxylate; Alternative to Example 6 above, (6bR, 1 OaS)-ethyl 3,6b,9, 10, 1 Oa- hexahydro-3-methyl-2-oxo-lH-pyrido[3′,4’:4,5]-pyrrolo[l,2,3-de]quinoxaline-8- carboxylate may also be made in a one pot method starting from Compound of Formula ID. A 2 liter 4 neck round bottom flask is equipped with a mechanical stirrer, reflux condenser, N2 inlet, teflon covered K-type temperature probe with a controller, and a heating mantle. To the flask is charged (4aS,9bR)-ethyl 6-bromo-3,4,4a,5-tetrahydro- lH-pyrido[4,3-b]indole-2(9bH)-carboxylate (250 g, 769 mmol), N-methyl chloroacetamide (124 g, 1153 mmol, 1.5 equiv), potassium iodide (191.5 g, 1160 mmol, 1.5 equiv), diisopropyl ethylamine (266 mL, 1531 mmol, 2.0 equiv), and dioxane (625 mL). The reaction is heated to reflux temperature of about 103 0C until less than 3% of the starting substrate is observed by HPLC (about 48 hours). Additional charge of N- methyl chloroacetamide and diisopropyl ethylamine maybe necessary. The reaction is then cooled to ca. 80 0C, and at this temperature copper iodide (29.2 g, 153.8 mmol, 0.2 equiv), potassium carbonate (232.5 g, 1682 mmol, 2.2 equiv), dimethylethylene diamine (49.6 mL, 461 mmol, 0.6 equiv), and additional dioxane (375 mL) is added. The reaction is then re-heated to reflux and is monitored by HPLC. Reflux occurs at ca. 103 0C. The reaction is monitored by HPLC.[0090] When complete, the reaction is cooled to ca. 40 0C and poured onto a plug of flash-grade silica gel (625 g, 2.5 g/g). It is eluted (under vacuum) with 6.25 L of ethyl acetate. The eluent is concentrated to a solid residue (320 gm), and then is dissolved in hot ethanol (800 ml). This mixture is allowed to cool to ambient temperature and stirred overnight. The next day it is cooled to 0-50C, aged for Ih and filtered. The cake is washed with cold ethanol (150 ml) and allowed to air dry to afford 170 grams (70%) of product as a white solid which is >99A% pure by HPLC. HPLC 10:90 to 90:10 CH3CN:H2O over 15 min. Hold at 90:10 for 2 min, 0.025% TFA Buffer, 1.5 mL/min, UV at 220 run, Phenomenex Jupiter Cl 8 column 4.6 mm x 250 mm. The product is 75A% pure by LC/MS in the total ion chromatogram. 1H-NMR (300MHz, CDCl3) 1.28(t, J= 6.9Hz, 3H), 1.86-1.96(m, 2H), 2.72(br, IH), 3.09-3.48(m, 7H), 3.86- 4.21(m, 5H), 6.75(dd, J= 1.2, 7.8Hz, IH), 6.82(t, J= 7.8Hz, IH), 6.90(dd, J= 1.2, 7.2Hz, IH).
1059630-08-8, The synthetic route of 1059630-08-8 has been constantly updated, and we look forward to future research findings.
Reference：
Patent; INTRA-CELLULAR THERAPIES, INC.; WO2008/112280; (2008); A1;,
Indole alkaloid derivatives as building blocks of natural products from?Bacillus thuringiensis?and?Bacillus velezensis?and their antibacterial and antifungal activity study
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles