-药物合成数据库

【药物名称】

化学结构式(Chemical Structure):

参考文献No.	54883
标题:	Isoxazole thrombin receptor antagonists
作者:	Freidinger, R.M.; Selnick, H.G.; Connolly, T.; Barrow, J.C.; Nantermet, P.G. (Merck & Co., Inc.)
来源:	GB 2356198

合成路线图解说明: The reaction of 1,3-benzodioxol-5-ylmethylamine (I) with acryloyl chloride (II) by means of TEA gives the acrylamide (III), which is reductocondensed with perhydroazepine (IV) by means of LiAlH4 or BH3/THF in THF to yield the secondary amine (V). Finally this compound is condensed with 5-chloro-3-(3,5-difluorophenyl)isoxazole (VI) by means of BuLi in diethyl ether to afford the target tertiary amine. The intermediate 5-chloro-3-(3,5-difluorophenyl)isoxazole (VI) has been obtained by two related ways: The condensation of 3.5-difluorobenzoyl chloride (VII) with malonic acid monoethyl ester (VIII) by means of BuLi gives 2-(3,5-difluorobenzoyl)acetic acid ethyl ester (IX), which is cyclized with hydroxylamine in HOAc to yield 3-(3,5-difluorophenyl)isoxazol-5-ol (X). Finally this compound is treated with POCl3 to afford the desired 5-chloro-3-(3,5-difluorophenyl)isoxazole (VI) intermediate. Alternatively, the reaction of 3,5-difluoroacetophenone (XI) with diethyl carbonate (XII) by means of NaH yields also the already reported intermediate 2-(3,5-difluorobenzoyl)acetic acid ethyl ester (IX)

参考文献No.	660562
标题:	Discovery of a nonpeptide small molecule antagonist of the human platelet thrombin receptor (PAR-1)
作者:	Nantermet, P.G.; Barrow, J.C.; Lundell, G.F.; Pellicore, J.M.; Rittle, K.E.; Young, M.; Freidinger, R.M.; Connolly, T.M.; Condra, C.L.; Karczewski, J.; Bednar, R.A.; Gaul, S.L.; Gould, R.J.; Prendergast, K.; Selnick, H.G.
来源:	Bioorg Med Chem Lett 2002,12(3),319

合成路线图解说明: The reaction of 1,3-benzodioxol-5-ylmethylamine (I) with acryloyl chloride (II) by means of TEA gives the acrylamide (III), which is reductocondensed with perhydroazepine (IV) by means of LiAlH4 or BH3/THF in THF to yield the secondary amine (V). Finally this compound is condensed with 5-chloro-3-(3,5-difluorophenyl)isoxazole (VI) by means of BuLi in diethyl ether to afford the target tertiary amine. The intermediate 5-chloro-3-(3,5-difluorophenyl)isoxazole (VI) has been obtained by two related ways: The condensation of 3.5-difluorobenzoyl chloride (VII) with malonic acid monoethyl ester (VIII) by means of BuLi gives 2-(3,5-difluorobenzoyl)acetic acid ethyl ester (IX), which is cyclized with hydroxylamine in HOAc to yield 3-(3,5-difluorophenyl)isoxazol-5-ol (X). Finally this compound is treated with POCl3 to afford the desired 5-chloro-3-(3,5-difluorophenyl)isoxazole (VI) intermediate. Alternatively, the reaction of 3,5-difluoroacetophenone (XI) with diethyl carbonate (XII) by means of NaH yields also the already reported intermediate 2-(3,5-difluorobenzoyl)acetic acid ethyl ester (IX)