【结 构 式】 |
【分子编号】12566 【品名】2-(1,3-benzodioxol-5-yloxy)ethyl methanesulfonate 【CA登记号】 |
【 分 子 式 】C10H12O6S 【 分 子 量 】260.26768 【元素组成】C 46.15% H 4.65% O 36.88% S 12.32% |
合成路线1
该中间体在本合成路线中的序号:(IX)Semotiadil fumarate has been obtained by several related ways: 1) The reaction of 2-(2-hydroxy-5-methoxyphenyl)-4-methyl-3,4-dihydro-2H-1,4-benzothiazin-3-one (I) with 3-chloropropyl bromide (II) by means of NaH in DMF gives 2-[2-(3-bromopropoxy)-5-methoxyphenyl]-4-methyl-3,4-dihydro-2H-1,4-benzothiazin-3-one (III) , which is condensed with N-[2-(1,3-benzodioxol-5-yloxy)ethyl]-N-methylamine (IV) by means of NaI in NaHCO3 in DMF yielding 2-[2-[3-[N-[2-(1,3-benzodioxol-5-yloxy)ethyl]-N-methylamino]propoxy]-5-methoxyphenyl]-4-methyl-3,4-dihydro-2H-1,4-benzothiazin-3-one (V). Finally, this compound is submitted to optical resolution by salification with L-(+)-2-hydroxy-2-phenylacetic acid (VI), fractional crystallization of the resulting salts, elimination of the chiral acid with NaHCO3 and salification with fumaric acid in ethanol. 2) Compound (V) can also be obtained by condensation of benzothiazinone (I) with N-[2-(1,3-benzodioxol-5-yloxy)ethyl]-N-(3-bromopropyl)-N-methylamine (VII) by means of NaH in DMF. 3) Compound (V) can also be obtained by condensation of 2-[5-methoxy-2-[3-(methylamino)propoxy]phenyl]-4-methyl-3,4-dihydro-2H-1,4-benzothiazin-3-one (VIII) with 2-(1,3-benzodioxol-5-yloxy)ethyl methanesulfonate (IX) by means of triethylamine in ethanol. 4) The optical resolution of the racemic compound (V) can also be performed by chromatography over a column packed with crystalline cellulose triacetate eluted with 95% ethanol.
【1】 Robinson, K.A.; Robinson, C.P.; Castaner, J.; Sesamodil Fumarate. Drugs Fut 1997, 22, 3, 229. |
【2】 Iwao, J.; Iso, T.; Oya, M. (Santen Pharmaceutical Co., Ltd.); Novel benzothiazine derivs.. EP 0237573; JP 1987123181; US 4786635; WO 8700838 . |
【3】 Yamauchi, H.; Kawashima, Y.; Yamamoto, K.; Ito, S.; Iwao, J.-I.; Fujita, M.; Ota, A.; Kato, N.; Synthesis and Ca2+ antagonistic activity of 2-[2-[(aminoalkyl)oxy]-5-methoxyphenyl]-3,4-dihydro-4-methyl-3-oxo-2H -1,4-benzothiazines. J Med Chem 1990, 33, 7, 1898-905. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 12558 | 2-(2-Hydroxy-5-methoxyphenyl)-4-methyl-2H-1,4-benzothiazin-3(4H)-one | C16H15NO3S | 详情 | 详情 | |
(II) | 10358 | 1-Bromo-3-chloropropane | 109-70-6 | C3H6BrCl | 详情 | 详情 |
(III) | 12560 | 2-[2-(3-Bromopropoxy)-5-methoxyphenyl]-4-methyl-2H-1,4-benzothiazin-3(4H)-one | C19H20BrNO3S | 详情 | 详情 | |
(IV) | 12561 | 2-(1,3-Benzodioxol-5-yloxy)-N-methyl-1-ethanamine; N-[2-(1,3-Benzodioxol-5-yloxy)ethyl]-N-methylamine | C10H13NO3 | 详情 | 详情 | |
(V) | 12562 | 2-(2-[3-[[2-(1,3-Benzodioxol-5-yloxy)ethyl](methyl)amino]propoxy]-5-methoxyphenyl)-4-methyl-2H-1,4-benzothiazin-3(4H)-one | C29H32N2O6S | 详情 | 详情 | |
(VI) | 12563 | (2S)-2-Hydroxy-2-phenylethanoic acid; S-(+)-Mandelic acid | 17199-29-0 | C8H8O3 | 详情 | 详情 |
(VII) | 12564 | N-[2-(1,3-Benzodioxol-5-yloxy)ethyl]-3-bromo-N-methyl-1-propanamine; N-[2-(1,3-Benzodioxol-5-yloxy)ethyl]-N-(3-bromopropyl)-N-methylamine | C13H18BrNO3 | 详情 | 详情 | |
(VIII) | 12565 | 2-[5-Methoxy-2-[3-(methylamino)propoxy]phenyl]-4-methyl-2H-1,4-benzothiazin-3(4H)-one | C20H24N2O3S | 详情 | 详情 | |
(IX) | 12566 | 2-(1,3-benzodioxol-5-yloxy)ethyl methanesulfonate | C10H12O6S | 详情 | 详情 |