2-(2-[3-[[2-(1,3-Benzodioxol-5-yloxy)ethyl](methyl)amino]propoxy]-5-methoxyphenyl)-4-methyl-2H-1,4-benzothiazin-3(4H)-one -Drug Synthesis Database

【结构式】

【分子编号】12562

【品名】2-(2-[3-[[2-(1,3-Benzodioxol-5-yloxy)ethyl](methyl)amino]propoxy]-5-methoxyphenyl)-4-methyl-2H-1,4-benzothiazin-3(4H)-one

【CA登记号】

【分子式】C₂₉H₃₂N₂O₆S

【分子量】536.64896

【元素组成】C 64.91% H 6.01% N 5.22% O 17.89% S 5.98%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(V)

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.

参考文献中间体

合成目标

【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

Extended Information