2-(2,3-dihydro-1,4-benzodioxin-5-yl{2-[(methylsulfonyl)oxy]ethyl}amino)ethyl methanesulfonate -Drug Synthesis Database

【结构式】

【分子编号】64786

【品名】2-(2,3-dihydro-1,4-benzodioxin-5-yl{2-[(methylsulfonyl)oxy]ethyl}amino)ethyl methanesulfonate

【CA登记号】

【分子式】C₁₄H₂₁NO₈S₂

【分子量】395.45468

【元素组成】C 42.52% H 5.35% N 3.54% O 32.37% S 16.22%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VI)

The intermediate dimesylate (VI) can be obtained as follows: The condensation of 2,3-dihydro-1,4-benzodioxin-5-amine (I) with ethyl bromoacetate (II) by means of Hunig's base and NaI in refluxing toluene gives the tertiary amine (III), which is reduced by means of LiAlH4 in THF to yield the diethanolamine (IV). Finally, this compound is esterified by means of mesyl chloride (V) to provide the desired dimesylate intermediate (VI). Alternatively, the diethanolamine (IV) can be obtained by direct condensation of 2,3-dihydro-1,4-benzodioxin-5-amine (I) with 2-chloroethanol (VII) by means of Hunig's base.

参考文献中间体

合成目标

【1】 Jirkovsky, I.; Zeldis, J.; Chan, A.W.-Y.; Fiegelson, G.B. (Wyeth); Preparation of N1-(2'-pyridyl)-1,2-propanediamine sulfamic acid and its use in the synthesis of biologically active piperazines. WO 0378396 .

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)	22000	2,3-dihydro-1,4-benzodioxin-5-amine; 2,3-dihydro-1,4-benzodioxin-5-ylamine; 5-Amino-1,4-benzodioxane	16081-46-2	C₈H₉NO₂	详情	详情
(II)	16640	Ethyl 2-bromoacetate; Ethyl bromoacetate	105-36-2	C₄H₇BrO₂	详情	详情
(III)	64784	ethyl 2-[2,3-dihydro-1,4-benzodioxin-5-yl(2-ethoxy-2-oxoethyl)amino]acetate		C₁₆H₂₁NO₆	详情	详情
(IV)	64785	2-[2,3-dihydro-1,4-benzodioxin-5-yl(2-hydroxyethyl)amino]-1-ethanol		C₁₂H₁₇NO₄	详情	详情
(V)	13467	Methanesulfonyl chloride;Mesyl chloride;Methylsulfonyl chloride;Methanesulfonic acid chloride;Methanesulfonyl chloride;Methanesulphonyl chloride	124-63-0	CH₃ClO₂S	详情	详情
(VI)	64786	2-(2,3-dihydro-1,4-benzodioxin-5-yl{2-[(methylsulfonyl)oxy]ethyl}amino)ethyl methanesulfonate		C₁₄H₂₁NO₈S₂	详情	详情
(VII)	10384	2-Chloro-1-ethanol; Ethylene chlorohydrin	107-07-3	C₂H₅ClO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

The reaction of 5(S)-methyl-3-phenyl-4,5-dihydro-3H-1,2,3-oxathiazol (VIII) with benzhydrylamine (IX) gives the sulfamic acid (X), which is deprotected by hydrogenation with H2 over Pd/C to yield N-(2(R)-aminopropyl-N-(2-pyridyl)sulfamic acid (XI). The hydrolysis of (XI) with 3N HCl affords N1-(2-pyridyl)propane-1,2(R)-diamine (XII). The cyclization of the intermediate dimesylate (VI) with sulfamic acid (XI) or diamine (XII) by means of K2CO3 and NaI in hot DMF or refluxing acetonitrile provides the disubstituted piperazine (XIII) (1), which is finally condensed with 4-cyanobenzoyl chloride (XIV) by means of K2CO3 in ethyl acetate to give the target benzamide (1,2).

参考文献中间体

合成目标

【1】 Kelly, M.G.; Childers, W.E.; Rosenzweig-Lipson, S.J. (Wyeth); Serotonergic agents. US 2002107254; US 6469007; WO 0244142 .
【2】 Jirkovsky, I.; Zeldis, J.; Chan, A.W.-Y.; Fiegelson, G.B. (Wyeth); Preparation of N1-(2'-pyridyl)-1,2-propanediamine sulfamic acid and its use in the synthesis of biologically active piperazines. WO 0378396 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	64786	2-(2,3-dihydro-1,4-benzodioxin-5-yl{2-[(methylsulfonyl)oxy]ethyl}amino)ethyl methanesulfonate		C₁₄H₂₁NO₈S₂	详情	详情
(VIII)	64787	(5S)-5-methyl-3-(2-pyridinyl)-1,2lambda~6~,3-oxathiazolidine-2,2-dione		C₈H₁₀N₂O₃S	详情	详情
(IX)	15149	alpha-Aminodiphenylmethane; diphenylmethanamine; benzhydrylamine	91-00-9	C₁₃H₁₃N	详情	详情
(X)	64788	(2R)-2-(benzhydrylamino)propyl(2-pyridinyl)sulfamic acid		C₂₁H₂₃N₃O₃S	详情	详情
(XI)	64789	(2R)-2-aminopropyl(2-pyridinyl)sulfamic acid		C₈H₁₃N₃O₃S	详情	详情
(XII)	64790	N-[(2R)-2-aminopropyl]-N-(2-pyridinyl)amine; (2R)-N~1~-(2-pyridinyl)-1,2-propanediamine		C₈H₁₃N₃	详情	详情
(XIII)	64791	N-{(2R)-2-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)-1-piperazinyl]propyl}-2-pyridinamine; N-{(2R)-2-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)-1-piperazinyl]propyl}-N-(2-pyridinyl)amine		C₂₀H₂₆N₄O₂	详情	详情
(XIV)	19280	4-cyanobenzoyl chloride	6068-72-0	C₈H₄ClNO	详情	详情

Extended Information