吡罗昔康EP杂质L(美洛昔康EP杂质F)

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

实验步骤: 投料: 取25ml单口瓶，加入C4X-173312-SM1和DMF/异丙醇，室温下加入碳酸钾，添加完毕后，反应液升至100℃下搅拌 LCMS监测（173312-s1-n），收率7%

实验步骤: 投料: 取25ml单口瓶，加入C4X-173312-SM1和DMF/异丙醇，室温下加入碳酸钾，添加完毕后，反应液升至100℃下搅拌 LCMS监测（173312-s1-n），2%含量，补加至0.5eq时，搅拌过夜，收率为15% 投平行反应

实验步骤: 投料: 取1L干燥三口瓶，加入C4X-173312-SM1和事先做好的异丙醇钠，氮气置换后，加入超干四氢呋喃，干冰乙醇浴下搅拌冷却后，用滴液漏斗滴加 1M LiHMDS，滴毕后，升至室温下搅拌过夜 LCMS监测（173312-s1-li-n），40%收率-

实验步骤: 投料: 取1L干燥三口瓶，加入C4X-173312-SM1（15g 1eq）和事先做好的异丙醇钠（60g 3eq 含量：21.7%），氮气置换后，加入超干四氢呋喃（210ml），干冰乙醇浴下搅拌冷却后，用滴液漏斗滴加 1M LiHMDS（212ml 4eq），滴加时间为1.2h，滴毕后，升至室温下搅拌过夜 LCMS监测（173312-s1-li-n），原料剩余少量，大部分转化为产物 后处理：反应液冰水浴下用饱和氯化铵淬灭，用6M 盐酸调节PH至7后，加入水（100ml）和乙酸乙酯（150ml）进行萃取，取有机相，水相再用乙酸乙酯（150ml*2）萃取，合并有机相并用无水硫酸钠干燥，抽滤，滤液减压浓缩得到黄色油状物。合并上一批次交付制备纯化

实验步骤: 投料: 取500ml单口瓶，加入C4X-173312-SM1（24g 1eq）和DMF（120ml）/异丙醇（100ml），室温下加入碳酸钾（11.71g 1eq），添加完毕后，反应液升至100℃下搅拌 LCMS监测（173312-s1-n），大部分为原料，产物占比少，将反应液分至3个封管中反应。 LCMS监测（173312-s1-2n），大部分为原料，直至反应一周后，产物占比13% 后处理：反应液将至室温，抽滤，得到红棕色澄清液，粗品直接经自动过柱机分离纯化（5%乙腈出原料和部分产物，50%乙腈出干净产物），得到红棕色固体1g 回收交叉层析液交付制备纯化 后续用下一批次方法，收率较高。

实验步骤: 投料: 取25ml单口瓶，加入C4X-173312-SM1和DMF/异丙醇，室温下加入碳酸钾，添加完毕后，反应液升至100℃下搅拌 LCMS监测（173312-s1-5eq-

实验步骤: 投料: 取25ml单口瓶，加入C4X-173312-SM1和DMF/异丙醇，室温下加入碳酸钾，添加完毕后，反应液升至100℃下搅拌 LCMS监测（173312-s1-0.5eq-n），含8%-9%

实验步骤: 投料: 取25ml单口瓶，加入C4X-173312-SM1和DMF/异丙醇，室温下加入碳酸钾，添加完毕后，反应液升至100℃下搅拌 LCMS监测（173312-s1-1eq-n），收率10%

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

实验步骤: A mixture of 74.3 g (0.25 mol) of isopropyl 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide and 25.7 g (0.32 mol) of 2-aminopyridine in 2,700 ml of xylene is maintained under reflux for 20 hours. During this time, approximately one third of the solvent is distilled off and is replaced, and finally the mixture is distilled to a final volume of 1,500 ml. The mixture is cooled to 0°-5° C. and filtered and the product washed with xylene. By crystallization with dichloroethane, 63 g (75%) of a crystalline white product, m.p. 198°-200° C. are obtained. is maintained under reflux for 20 hours During this time, approximately one third of the solvent is distilled off finally the mixture is distilled to a final volume of 1,500 ml The mixture is cooled to 0°-5° C. filtered the product washed with xylene By crystallization with dichloroethane, 63 g (75%) of a crystalline white product, m.p. 198°-200° C. are obtained

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

实验步骤: A mixture of 74.3 g (0.25 mol) of isopropyl 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide and 25.7 g (0.32 mol) of 2-aminopyridine in 2,700 ml of xylene is maintained under reflux for 20 hours. During this time, approximately one third of the solvent is distilled off and is replaced, and finally the mixture is distilled to a final volume of 1,500 ml. The mixture is cooled to 0°-5° C. and filtered and the product washed with xylene. By crystallization with dichloroethane, 63 g (75%) of a crystalline white product, m.p. 198°-200° C. are obtained. is maintained under reflux for 20 hours During this time, approximately one third of the solvent is distilled off finally the mixture is distilled to a final volume of 1,500 ml The mixture is cooled to 0°-5° C. filtered the product washed with xylene By crystallization with dichloroethane, 63 g (75%) of a crystalline white product, m.p. 198°-200° C. are obtained