4-[4-[(5S)-5-(Aminomethyl)-2-oxo-3-oxazolidinyl]phenyl]-3-morpholinone Hydrochloride

12.I-4-(4-aminophenyl)-3-morpholinone (1) ye-anticoagulant rivaroxaban yalungiswa ngeendlela ezimbini: ①Bromobenzene yaphendulwa ngokulandelelana nge-ethanolamine kunye ne-chloroacetyl chloride ukufumana i-4-benzene I-morpholinone yokunciphisa i-nitrated ke. I-1, kwaye isivuno siphelele malunga ne-32%;②I-Bromobenzene iqale ifakwe i-nitrate, kwaye emva koko isebenze nge-ethanolamine ukufumana i-2-(4-nitroanilino)thanol, ethi emva koko ivalwe nge-chloroacetyl chloride.Ukusabela kokunciphisa kuvelisa i-1, kwaye isivuno siphelele malunga ne-47%.

I-Rivaroxaban luhlobo olutsha lwe-anticoagulant olunokuthi luthathwe ngokuthe ngqo ngomlomo.Ivimbela ngokuthe ngqo ukusebenza kwe-coagulation factor Xa, inesiphumo esicacileyo se-anticoagulant, ayifuni ukubeka iliso ngokuqhubekayo, kwaye inokhuseleko oluphezulu.Ngokusetyenziswa kweklinikhi ye-rivaroxaban, Imfuno ye-rivaroxaban iya kwanda ngokuthe ngcembe.Igama lekhemikhali ye-rivaroxaban yi-5-chloro-N- (((5S) -2-oxo-3-[4- (3-oxo- 4-morpholinyl) phenyl) -1,3-oxazolidine-5-yl) methyl -2-thiophenecarboxamide.Okwangoku kukho iindlela ezimbini zokwenziwa ezichazwe kwiincwadi, kwaye zombini iindlela zisetyenziswa I-4-(4-aminophenyl) ephakathi -3-morpholinone.Nangona kukho iingxelo malunga nokuhlanganiswa kwe-4- (4-aminophenyl) -3-morpholinone ekhaya nakwamanye amazwe, kukho ixabiso eliphezulu lokuphendula izinto eziluhlaza.Iphezulu, kunzima ukuyithenga, okanye iimfuno zokusebenza zokusabela ziphezulu kakhulu, kunzima ukuzibamba, azihambisani nokukhuselwa kokusingqongileyo kunye nezinye iintsilelo, kwaye azihlangabezani neemfuno zemveliso enkulu yoshishino.Lungiselela i-key intermediate ye-rivaroxaban 4- (4-aminophenyl)- Inkqubo yokuvelisa i-3-morpholinone kunye nokunciphisa ixabiso lezinto ezibonakalayo ngokuqinisekileyo ziya kukhuthaza ukukhuthazwa kunye nokusetyenziswa kwe-rivaroxaban.Akukho ngxelo malunga nokuhlanganiswa kwe-rivaroxaban e-China.Sise-rivaroxaban Isitshixo esiphakathi kwe-4- (4-aminophenyl) -3-morpholinone indlela yokwenziwa kunye neteknoloji iye yafundwa ngokutsha.Iibromobenzene ezimbini kunye ne-p-nitrobromobenzene njengezixhobo zokuqalisa ziyacetywa.Indlela yenkqubo.Gxininisa kwinkqubo ye-cyclization ye-3-morpholinone ring.