I-8-Bromo-7-kodwa-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3

Ukuhlalutya i-linagliptin ekhoyo kunye nesitshixo sayo esiphakathi kwe-8-bromo-7-(2-butynyl)-3,7-dihydro-3-methyl-1--[(4-methyl -2-quinazolinyl)methyl)-1H-purine- I-2,6-dione (11) indlela yokudibanisa, fumana indlela yokwenziwa ilungele imveliso yoshishino.Indlela: shwankathela iindlela ezahlukeneyo zokwenziwa.Iziphumo kunye nezigqibo: Umzila 2.2 unenkqubo elula kunye neendleko eziphantsi, ezifanelekileyo ngakumbi kwimveliso yoshishino.

I-8-bromo-3,7-dihydro-3-methyl-1H-purine-2,6-dione yinto ephambili ephakathi kwi-synthesis ye-hypoglycemic drug linagliptin.I-synthesis ye-1 isebenzisa i-methyl urea kunye ne-cyanoacetic acid njengezinto zokuqala, kwaye ithatha amanyathelo amathandathu e-condensation, i-cyclization, i-nitrosation, ukunciphisa, i-cyclization, kunye ne-bromine kunye nesivuno esipheleleyo se-46.3%.Izakhiwo zabo bonke abaphakathi ziqinisekiswe yi-1HNMR.

Ukuveliswa kwangoku kuhambelana nendlela elula yokulungiselela i-high-purity linagliptin.I-Quinazoline, i-key intermediate yokulungiselela imbiza enye ye-linagliptin 8 bromo 7 (2 butyne 1 base) 3,7 dihydro 3 methyl 1 [(4 methyl 2 quinazolinyl) methyl] 1H Purine 2,6 dione, i-intermediate ihlukaniswe ukuhluzwa, kwaye emva koko yasabela nge-(R)3 aminopiperidine dihydrochloride ukufumana isisombululo esiqulethe i-linagliptin.Emva kokuba isisombululo esiqulathe i-linagliptin sicutshungulwe kwakhona, iDeliraliptin imveliso esulungekileyo.Ukulungiswa kwe-key intermediate ye-invention yangoku yamkela indlela yembiza enye, ekulungele ukusebenza kunye nokuphucula isivuno.Emva kokuba i-intermediate engundoqo ihlulwe, iphendulwa nge (R) i-3 aminopiperidine dihydrochloride, ngaloo ndlela Ukufumana i-linagliptin ephezulu yokucoca iphinda ihlangabezane neemfuno zokuvelisa kunye nokubhengezwa kweenkampani zamachiza ukuya kwinqanaba elikhulu.