阿普斯特杂质68

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To prepare the required acid chloride, 27.77 g of 2-chloro-5-thiophenecarboxylic acid (0.171 mol) are suspended in 50 ml of thionyl chloride (0.685 mol) and stirred at 90° C. for 90 min (after 15 min, a clear solution is formed). The resulting solution is concentrated under reduced pressure, twice subjected to azeotropic distillation with toluene, dissolved in 60 ml of toluene and, over a period of 40 min and at 20° C., added dropwise to a solution of 17.98 g (110.2 mmol) of 3-aminophthalic anhydride in 200 ml of pyridine. The mixture is stirred at RT overnight, the pyridine is evaporated under reduced pressure and the residue is twice stirred with toluene and re-evaporated. 11 of ethyl acetate and 0.51 of KH2PO4 buffer (pH=4–5) are added and the mixture is then shaken vigorously and filtered off with suction, and the solids are washed with ethyl acetate, pressed thoroughly dry and dried under reduced pressure over P2O5. The mother liquor is extracted three times with ethyl acetate and evaporated and the residue is stirred with ethyl acetate and filtered off with suction. This gives a total of 19.77 g (58.3% of theory) of the target compound of m.p. 195° C. a clear solution is formed) The resulting solution is concentrated under reduced pressure twice subjected to azeotropic distillation with toluene dissolved in 60 ml of toluene and, over a period of 40 min and at 20° C. The mixture is stirred at RT overnight the pyridine is evaporated under reduced pressure the residue is twice stirred with toluene re-evaporated 11 of ethyl acetate and 0.51 of KH2PO4 buffer (pH=4–5) are added the mixture is then shaken vigorously filtered off with suction the solids are washed with ethyl acetate pressed thoroughly dry dried under reduced pressure over P2O5 The mother liquor is extracted three times with ethyl acetate evaporated the residue is stirred with ethyl acetate filtered off with suction This gives a total of 19.77 g (58.3% of theory) of the target compound of m.p. 195° C.

实验步骤: 投料: 向25 mL单口瓶中加入SM（0.16 g，1.00 mmol，1.00 eq），尿素（0.18 g，3.00 mmol，3.00eq）和DMF（2.00 mL，C=0.50 M），粉末溶解澄清，110℃反应。\n监测: 反应1.5 h后，LCMS监测，没有产物MS，只有原料的MS，继续110℃反应，过夜。 第二天，LCMS监测，没有产物MS，只有原料的MS。

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

实验步骤: 500 mg (3.1 mmol) 4-amino-isobenzofuran-1,3-dione and 1.13 g (3.1 mmol) (ethoxy-carbonylmethylene)-triphenylphosphorane are dissolved in 5 ml of tetrahydrofuran (THF) and refluxed for 3 h. Then the solvent is eliminated in vacuo. The crude product is purified by column chromatography. The carrier used is silica gel and the eluant used is a mixture of cyclohexane:ethyl acetate (75:25). refluxed for 3 h The crude product is purified by column chromatography a mixture of cyclohexane:ethyl acetate (75:25)

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To prepare the required acid chloride, 27.77 g of 2-chloro-5-thiophenecarboxylic acid (0.171 mol) are suspended in 50 ml of thionyl chloride (0.685 mol) and stirred at 90° C. for 90 min (after 15 min, a clear solution is formed). The resulting solution is concentrated under reduced pressure, twice subjected to azeotropic distillation with toluene, dissolved in 60 ml of toluene and, over a period of 40 min and at 20° C., added dropwise to a solution of 17.98 g (110.2 mmol) of 3-aminophthalic anhydride in 200 ml of pyridine. The mixture is stirred at RT overnight, the pyridine is evaporated under reduced pressure and the residue is twice stirred with toluene and re-evaporated. 1 l of ethyl acetate and 0.5 l of KH2PO4 buffer (pH=4-5) are added and the mixture is then shaken vigorously and filtered off with suction, and the solids are washed with ethyl acetate, pressed thoroughly dry and dried under reduced pressure over P2O5. The mother liquor is extracted three times with ethyl acetate and evaporated and the residue is stirred with ethyl acetate and filtered off with suction. This gives a total of 19.77 g (58.3% of theory) of the target compound of m.p. 195° C. a clear solution is formed) The resulting solution is concentrated under reduced pressure twice subjected to azeotropic distillation with toluene dissolved in 60 ml of toluene and, over a period of 40 min and at 20° C. The mixture is stirred at RT overnight the pyridine is evaporated under reduced pressure the residue is twice stirred with toluene re-evaporated 1 l of ethyl acetate and 0.5 l of KH2PO4 buffer (pH=4-5) are added the mixture is then shaken vigorously filtered off with suction the solids are washed with ethyl acetate pressed thoroughly dry dried under reduced pressure over P2O5 The mother liquor is extracted three times with ethyl acetate evaporated the residue is stirred with ethyl acetate filtered off with suction This gives a total of 19.77 g (58.3% of theory) of the target compound of m.p. 195° C.

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To prepare the required acid chloride, 27.77 g of 2-chloro-5-thiophenecarboxylic acid (0.171 mol) are suspended in 50 ml of thionyl chloride (0.685 mol) and stirred at 90° C. for 90 min (after 15 min, a clear solution is formed). The resulting solution is concentrated under reduced pressure, twice subjected to azeotropic distillation with toluene, dissolved in 60 ml of toluene and, over a period of 40 min and at 20° C., added dropwise to a solution of 17.98 g (110.2 mmol) of 3-aminophthalic anhydride in 200 ml of pyridine. The mixture is stirred at RT overnight, the pyridine is evaporated under reduced pressure and the residue is twice stirred with toluene and re-evaporated. 11 of ethyl acetate and 0.51 of KH2PO4 buffer (pH=4–5) are added and the mixture is then shaken vigorously and filtered off with suction, and the solids are washed with ethyl acetate, pressed thoroughly dry and dried under reduced pressure over P2O5. The mother liquor is extracted three times with ethyl acetate and evaporated and the residue is stirred with ethyl acetate and filtered off with suction. This gives a total of 19.77 g (58.3% of theory) of the target compound of m.p. 195° C. a clear solution is formed) The resulting solution is concentrated under reduced pressure twice subjected to azeotropic distillation with toluene dissolved in 60 ml of toluene and, over a period of 40 min and at 20° C. The mixture is stirred at RT overnight the pyridine is evaporated under reduced pressure the residue is twice stirred with toluene re-evaporated 11 of ethyl acetate and 0.51 of KH2PO4 buffer (pH=4–5) are added the mixture is then shaken vigorously filtered off with suction the solids are washed with ethyl acetate pressed thoroughly dry dried under reduced pressure over P2O5 The mother liquor is extracted three times with ethyl acetate evaporated the residue is stirred with ethyl acetate filtered off with suction This gives a total of 19.77 g (58.3% of theory) of the target compound of m.p. 195° C.