2-butyl-1-benzofuran-5-amine

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: This method is very simple and economical as regards the number of the reaction steps. Its drawback is, however, that in the last step the hydrochloride salt of dronedarone is obtained in a rather contaminated form. This can be explained by the presence of the dibutylamino-propyl group in the Friedel-Crafts reaction. In the examples of WO02/48132 the yield is 90%, during the purification steps at first the raw dronedarone hydrochloride salt, then following treatment with hydrogen chloride solution in isopropanol, the purified dronedarone hydrochloride salt is obtained (90%). It means that the yield of the raw dronedarone hydrochloride is 90% and then the purification step has a yield of 90%. Another drawback of the method is that the reactants used in the Friedel-Crafts reaction and the obtained by-products are insoluble in water, thus they cannot be removed from the system by aqueous washing. the purification step used in the Friedel-Crafts reaction thus they cannot be removed from the system by aqueous washing

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Patent application WO0248132 describes a method for the synthesis of dronedarone using 2-n-butyl-5-nitro-benzofuran which is reduced, under pressure, with hydrogen in the presence of platinum oxide as catalyst in order to form 2-n-butyl-5-amino-benzofuran. This benzofuran derivative is then subjected to the action of methanesulfonyl chloride, which gives 2-n-butyl-5-methanesulfonamido-benzofuran which is treated with 4-[3-(di-n-butylamino)-propoxy]-benzoyl chloride to give dronedarone.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Patent application WO0248132 describes a method for the synthesis of dronedarone using 2-n-butyl-5-nitro-benzofuran which is reduced, under pressure, with hydrogen in the presence of platinum oxide as catalyst in order to form 2-n-butyl-5-amino-benzofuran. This benzofuran derivative is then subjected to the action of methanesulfonyl chloride, which gives 2-n-butyl-5-methanesulfonamido-benzofuran which is treated with 4-[3-(di-n-butylamino)-propoxy]-benzoyl chloride to give dronedarone.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A process for synthesizing dronedarone was described in patent application WO 02/48132, mentioned previously, using 2-n-butyl-5-nitrobenzofuran, which is reduced, under pressure with hydrogen in the presence of platinum oxide as catalyst to form 2-n-butyl-5-aminobenzofuran. This benzofuran derivative is then subjected to the action of methanesulfonyl chloride, which gives 2-n-butyl-5-methanesulfonamidobenzofuran, which is treated with 4-[3-(di-n-butylamino)propoxy]benzoyl chloride to obtain dronedarone.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A process for synthesizing dronedarone was described in patent application WO 02/48132, mentioned previously, using 2-n-butyl-5-nitrobenzofuran, which is reduced, under pressure with hydrogen in the presence of platinum oxide as catalyst to form 2-n-butyl-5-aminobenzofuran. This benzofuran derivative is then subjected to the action of methanesulfonyl chloride, which gives 2-n-butyl-5-methanesulfonamidobenzofuran, which is treated with 4-[3-(di-n-butylamino)propoxy]benzoyl chloride to obtain dronedarone.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A process for synthesizing dronedarone was described in patent application WO 02/48132, mentioned previously, using 2-n-butyl-5-nitrobenzofuran, which is reduced, under pressure with hydrogen in the presence of platinum oxide as catalyst to form 2-n-butyl-5-aminobenzofuran. This benzofuran derivative is then subjected to the action of methanesulfonyl chloride, which gives 2-n-butyl-5-methanesulfonamidobenzofuran, which is treated with 4-[3-(di-n-butylamino)propoxy]benzoyl chloride to obtain dronedarone.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 100 g of 5-amino-2-butylbenzofuran, 192 ml of tetrahydrofuran and 96 ml of methyl tert-butyl ether are introduced into a round-bottomed flask. 59.35 g of methanesulfonyl chloride are added, at 20° C., followed by 43.23 g of 20% aqueous ammonia. 44.51 g of methanesulfonyl chloride are then introduced, followed by 86.47 g of 20% aqueous ammonia. 48 ml of water are then added, the medium is separated by settling and the organic phase is washed twice with 211 g of 10% aqueous sodium chloride solution. The medium is separated by settling and concentrated at 400° C. under vacuum, to give the desired compound in crude form (weight yield: 100%). the medium is separated the organic phase is washed twice with 211 g of 10% aqueous sodium chloride solution The medium is separated concentrated at 400° C. under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: This method is very simple and economical as regards the number of the reaction steps. Its drawback is, however, that in the last step the hydrochloride salt of dronedarone is obtained in a rather contaminated form. This can be explained by the presence of the dibutylamino-propyl group in the Friedel-Crafts reaction. In the examples of WO02/48132 the yield is 90%, during the purification steps at first the raw dronedarone hydrochloride salt, then following treatment with hydrogen chloride solution in isopropanol, the purified dronedarone hydrochloride salt is obtained (90%). It means that the yield of the raw dronedarone hydrochloride is 90% and then the purification step has a yield of 90%. Another drawback of the method is that the reactants used in the Friedel-Crafts reaction and the obtained by-products are insoluble in water, thus they cannot be removed from the system by aqueous washing. the purification step used in the Friedel-Crafts reaction thus they cannot be removed from the system by aqueous washing

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Patent application WO0248132 describes a method for the synthesis of dronedarone using 2-n-butyl-5-nitro-benzofuran which is reduced, under pressure, with hydrogen in the presence of platinum oxide as catalyst in order to form 2-n-butyl-5-amino-benzofuran. This benzofuran derivative is then subjected to the action of methanesulfonyl chloride, which gives 2-n-butyl-5-methanesulfonamido-benzofuran which is treated with 4-[3-(di-n-butylamino)-propoxy]-benzoyl chloride to give dronedarone.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Patent application WO0248132 describes a method for the synthesis of dronedarone using 2-n-butyl-5-nitro-benzofuran which is reduced, under pressure, with hydrogen in the presence of platinum oxide as catalyst in order to form 2-n-butyl-5-amino-benzofuran. This benzofuran derivative is then subjected to the action of methanesulfonyl chloride, which gives 2-n-butyl-5-methanesulfonamido-benzofuran which is treated with 4-[3-(di-n-butylamino)-propoxy]-benzoyl chloride to give dronedarone.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A process for synthesizing dronedarone was described in patent application WO 02/48132, mentioned previously, using 2-n-butyl-5-nitrobenzofuran, which is reduced, under pressure with hydrogen in the presence of platinum oxide as catalyst to form 2-n-butyl-5-aminobenzofuran. This benzofuran derivative is then subjected to the action of methanesulfonyl chloride, which gives 2-n-butyl-5-methanesulfonamidobenzofuran, which is treated with 4-[3-(di-n-butylamino)propoxy]benzoyl chloride to obtain dronedarone.