1,2,3,9-四氢咔唑-4-酮

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of 1,2,3,9-tetrahydro-4H-carbazol-4-one (6.02 g, 32.5 mmol) in 1:1 ethylene glycol: p-dioxane (100 mL) at 80° C. is added copper (II) chloride (21 g, 156.2 mmol). The mixture is heated for 20 minutes. The mixture is then partitioned between water and ethyl acetate. The layers are separated and the organic layer is washed three times with water (200 mL). The organic layer is dried over anhydrous sodium sulfate, filtered, and concentrated. The residue is dissolved in DMF (100 mL) to which is added lithium bromide (7.04 g, 81.25 mmol) and lithium carbonate (6.0 g, 81.25 mmol). The mixture is heated at 120° C. for 4.5 hours. The mixture is then partitioned between water and ether. The ether layer is washed three times with water (200 mL). The ether layer is dried over anhydrous sodium sulfate, filtered and concentrated. Column chromatography, silica gel (800 mL), using CH2Cl2 as eluent gave 1.1 g (18%) of the title compound; 1H NMR (CDCl3) δ5.26, 6.57, 7.01, 7.26, 7.41, 8.05, 8.26; Anal. Calcd for C12H9NO: C, 78.67; H, 4.95; N, 7.64. Found: C, 78.04; H, 4.94; N, 7.58. The mixture is heated for 20 minutes The mixture is then partitioned between water and ethyl acetate The layers are separated the organic layer is washed three times with water (200 mL) The organic layer is dried over anhydrous sodium sulfate filtered concentrated The residue is dissolved in DMF (100 mL) to which The mixture is then partitioned between water and ether The ether layer is washed three times with water (200 mL) The ether layer is dried over anhydrous sodium sulfate filtered concentrated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 1,3-cyclohexane dione (1.99 g, 17.7 mmol) in water (55 mL) is added phenylhydrazine (1.92 g, 17.7 mmol) in 10 mL of water. A gummy solid quickly formed, which after completion of the addition is scrapped with a spatula to give a solid. The solid is collected, washed with water, and dried in a vacuum oven to give 3.0 g of a tan solid. After drying, the tan solid is stirred at reflux in TFA (25 mL) overnight. Upon cooling, TFA is removed in vacuo and water is added to the residue. The resulting solid is collected, washed with water, and dried to give 1.82 g (55%) of the title compound; mp 218-220° C.; IR (drift) 3150, 3130, 3104, 3093, 3056, 2976, 2954, 2944, 1607, 1577, 1466, 1413, 1251, 1178, 755 cm−1; 1H NMR (CDCl3) δ2.26, 2.64, 3.00, 7.26, 7.35, 8.21, 8.74. Anal. Calcd for C12H11NO: C, 77.81; H, 5.99; N, 7.56. Found: C, 77.82; H, 6.15; N, 7.54. A gummy solid quickly formed which after completion of the addition to give a solid The solid is collected washed with water dried in a vacuum oven

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a reactor containing water (1 L) was added Raney nickel (35 g) followed by 1,2,3,9-tetrahydrocarbazole-4-one (50 g) and sodium hydroxide (15 g). The contents were heated to reflux and maintained for about 20 hours. The catalyst was filtered off and the filtrate was acidified to obtain a solid, which was filtered and dried to obtain the title compound. When necessary, the title compound was further purified by dissolving in 10% sodium hydroxide solution, treating with activated charcoal and precipitation from dilute hydrochloric acid to give off-white to grey crystals of 4-hydroxy carbazole in 50% yield. The contents were heated to reflux maintained for about 20 hours The catalyst was filtered off to obtain a solid, which was filtered dried

实验步骤: 投料: 10.15 11:00 将原料SM1（15g,80mmol,1eq)加入反应瓶中，无水乙醇溶解，加入多聚甲醛(24.3g,810mmol,10eq),盐酸二甲胺（66g,810mmol,10eq),加入完毕加热至回流（78℃）反应。 10.16 9：30 LCMS(13949-1-1-GY) 有产物生成，有部分原料未转化，继续反应。 10.17 9：30 LCMS(13949-1-1-2GY) 大部分原料转为产物，仍有少量原料，继续反应 17：00 LCMS(13949-1-1-2GY-2) 与上午LCMS相差不大，停止反应。 该批反应时间长且原料转化不完全，换方法做，该批不做处理，待用。

实验步骤: 投料: 10.16 10:20 将原料SM1（20g,108mmol,1eq）加入500ml三口瓶中，加入甲苯（40ml），冰醋酸（160ml）（1:4），搅拌下加入多聚甲醛（4.2g,140.4mmol,1.3eq）二甲胺盐酸盐（10.6g,129.6mmol,1.2eq）,加入完毕110℃加热反应。 13:00 LCMS(13949-1-3-3H) 主峰为产物峰，原料基本消耗完，停止反应。 后处理 待体系冷却至室温，减压浓缩后加甲醇（80ml）溶解，用饱和碳酸钠溶液调PH至9，再浓缩除去甲醇，加水（150ml），EA（250ml）萃取，两相中有固体不溶，过滤，滤饼用EA洗涤，固体为较干净产物，收集滤液，将有机相分出，水相再萃取一次，合并有机相，饱和食盐水洗，无水硫酸钠干燥，减压浓缩除去溶剂后用EA（60ml）打浆，过滤收集固体，共得19.5g黄褐色产物。

实验步骤: 投料: 10.15 12:00 将原料SM1（2g,10.7mmol,1eq）加入100ml三口瓶中，加入甲苯（5ml），冰醋酸（20ml）（1:4），搅拌下加入多聚甲醛（0.42g,13.9mmol,1.3eq）二甲胺盐酸盐（1.04g,12.8mmol,1.2eq）,加入完毕110℃加热反应。 14:00 LCMS(13949-1-2-2H)主峰为产物峰，仍有少量原料剩余。 TLC（DCM:MeOH=10:1）有较原料极性大的点生成，仍有少量原料点。 1h后 后处理 待体系冷却至室温后减压浓缩，得褐色油状直接用于下一步反应。

实验步骤: 投料: 将(3 g,1.0 eq。）1,2,3,4-Tetrahydro-4-oxocarbazole加到 80 ml无水乙醇，加热至回流，分批加人不同比例的多聚甲醛（4.8 g,10 eq.）与盐酸二甲胺（13.21 g,10 eq.）的混合物。加完后继续回流72小时。\n监测: TLC显示反应有新点产生，LCMS也找到了产品。有30%原料剩余\n后处理: 冷却，用2mol盐酸调至 PH=1,以乙酸乙酯萃取,水层用固体 Na2CO3, 中和至 PH=9,再以乙殷乙脂萃取，合并有机层，用无水硫酸镁干燥.\n纯化: 正向纯化：DCM/MeOH=10/1,洗脱梯度：DCM；DCM/MeOH=50/1;DCM/MeOH=30/1;DCM/MeOH=20/1;DCM/MeOH=10/1,得纯品 1.83 g

实验步骤: 投料: 将（0.3 g,1.0 eq。）1,2,3,4-Tetrahydro-4-oxocarbazole加到 8 ml无水乙醇，加热至回流，分批加人不同比例的多聚甲醛（0.48 g,10 eq.）与盐酸二甲胺（1.3 g,10 eq.）的混合物。加完后继续回流72小时。\n监测: TLC显示反应有新点产生，LCMS也找到了产品。\n纯化: 正向纯化：DCM/MeOH=10/1,洗脱梯度：DCM；DCM/MeOH=50/1;DCM/MeOH=30/1;DCM/MeOH=20/1;DCM/MeOH=10/1,得纯品 160 mg\n后处理: 冷却，用2mol盐酸调至 PH=1,以乙酸乙酯萃取,水层用固体 Na2CO3, 中和至 PH=9,再以乙殷乙脂萃取，合并有机层，用无水硫酸镁干燥.

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 0.25 mol/L 1,3-cyclohexanedione/50% sulfuric acid solution was placed in a 200-mL container purged with nitrogen. Then, a 0.25 mol/L phenylhydrazine/50% sulfuric acid solution was added dropwise into the container under stirring at 20000 rpm by CLEARMIX (manufactured by M Technique Co., Ltd.) while the temperature of the liquid in the container was maintained at 25° C. As a result of HPLC analysis, the production rate of 1,2,3,4-tetrahydrocarbazol-4-one was 24% or less. purged with nitrogen Then, a 0.25 mol/L phenylhydrazine/50% sulfuric acid solution was added dropwise into the container As a result of HPLC analysis

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 0.25 mol/L 1,3-cyclohexanedione/50% sulfuric acid solution was sent as a first fluid from the center at a ratio of supply pressure/back pressure of 0.07 MPa/0.02 MPa, a rotation speed of 500 rpm, and a sending temperature of 25° C., and a 0.25 mol/L phenylhydrazine/50% sulfuric acid solution was introduced as a second fluid into a space between the processing surfaces at 18 mL/min. The first fluid and the second fluid were mixed in a thin film fluid, and then a solution obtained after processing was discharged from the space between the processing surfaces at 29 mL/min. As a result of HPLC analysis, the production rate of 1,2,3,4-tetrahydrocarbazol-4-one was 80% or higher. The first fluid and the second fluid were mixed in a thin film fluid a solution obtained after processing As a result of HPLC analysis

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a 500 ml two-neck flask, 1,2,3,4-tetrahydro-9H-carbazole-4-one (Compound E, 20 g), t-butyl bromobenzene (60 g), potassium carbonate (43 g), Cu powder (2.1 g), and NMP (70 ml) were mixed and stirred. The reaction mixture was refluxed and stirred for 24 to 30 hours in a state in which the temperature was raised. When the reaction was completed, the reactant was cooled at room temperature, and then the reactant was mixed with ethylacetate (500 ml) and brine (500 ml) and strongly stirred. Floating materials was filtered and removed using celite, and the organic layer was separated. The water layer was extracted using ethylacetate, and the organic layer was collected and dried over magnesium sulfate. The organic layer was concentrated, and the residual was purified using a column chromatography, thereby obtaining 13 g of N-(t-butylphenyl) carbazolone (Compound F). The reaction mixture was refluxed stirred for 24 to 30 hours in a state in which the temperature was raised strongly stirred Floating materials was filtered removed the organic layer was separated The water layer was extracted the organic layer was collected dried over magnesium sulfate The organic layer was concentrated the residual was purified

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of 1,2,3,9-tetrahydro-4H-carbazol-4-one (6.02 g, 32.5 mmol) in 1:1 ethylene glycol: p-dioxane (100 mL) at 80° C. is added copper (II) chloride (21 g, 156.2 mmol). The mixture is heated for 20 minutes. The mixture is then partitioned between water and ethyl acetate. The layers are separated and the organic layer is washed three times with water (200 mL). The organic layer is dried over anhydrous sodium sulfate, filtered, and concentrated. The residue is dissolved in DMF (100 mL) to which is added lithium bromide (7.04 g, 81.25 mmol) and lithium carbonate (6.0 g, 81.25 mmol). The mixture is heated at 120° C. for 4.5 hours. The mixture is then partitioned between water and ether. The ether layer is washed three times with water (200 mL). The ether layer is dried over anhydrous sodium sulfate, filtered and concentrated. Column chromatography, silica gel (800 mL), using CH2Cl2 as eluent gave 1.1 g (18%) of the title compound; 1H NMR (CDCl3) δ5.26, 6.57, 7.01, 7.26, 7.41, 8.05, 8.26; Anal. Calcd for C12H9NO: C, 78.67; H, 4.95; N, 7.64. Found: C, 78.04; H, 4.94; N, 7.58. The mixture is heated for 20 minutes The mixture is then partitioned between water and ethyl acetate The layers are separated the organic layer is washed three times with water (200 mL) The organic layer is dried over anhydrous sodium sulfate filtered concentrated The residue is dissolved in DMF (100 mL) to which The mixture is then partitioned between water and ether The ether layer is washed three times with water (200 mL) The ether layer is dried over anhydrous sodium sulfate filtered concentrated