D-t-EtDO-P4, -Drug Synthesis Database

【结构式】

【药物名称】D-t-EtDO-P4

【化学名称】N-[(1R,2R)-2-(2,3-Dihydro-1,4-benzodioxin-6-yl)-2-hydroxy-1-(1-pyrrolidinylmethyl)ethyl]hexadecanamide

【CA登记号】245329-78-6

【分子式】C₃₁H₅₂N₂O₄

【分子量】516.77109

【开发单位】National Institutes of Health (Originator), University of Michigan (Originator)

【药理作用】Fabry's Disease, Agents for, METABOLIC DRUGS, Therapy of Inborn Errors of Metabolism

合成路线1 合成路线2

合成路线1

Methenamine is added to a solution of bromide (I) in CHCl3 and after treatment with concentrated HCl, amine (II) is obtained. NaOAc and palmitoyl chloride (III) are added to a solution of (II) in THF to yield derivative (IV) which is finally converted to (V) by treatment with paraformaldehyde and pyrrolidine in ethanol, followed by treatment with concentrated HCl, reduction with NaBH4 and final hydrolysis with diluted HCl.

参考文献中间体

【1】 Lee, L.; et al.; Improved inhibitors of glucosylceramide synthase. J Biol Chem 1999, 274, 21, 14662.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	11376	Pyrrolidine	123-75-1	C₄H₉N	详情	详情
(I)	41363	2,3-dihydro-1,4-benzodioxine-6-carbonyl bromide		C₉H₇BrO₃	详情	详情
(II)	41364	2-amino-1-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-ethanone		C₁₀H₁₁NO₃	详情	详情
(III)	16480	Palmitoyl Chloride; hexadecanoyl chloride	112-67-4	C₁₆H₃₁ClO	详情	详情
(IV)	41365	N-[2-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-oxoethyl]hexadecanamide		C₂₆H₄₁NO₄	详情	详情
(V)	65179	N-[(2R)-2-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-hydroxy-1-(1-pyrrolidinylmethyl)ethyl]hexadecanamide		C₃₁H₅₂N₂O₄	详情	详情

合成路线2

The condensation of 2,3-dihydrobenzodioxin-6-carbaldehyde (I) with 5(S)-phenylmorpholin-2-one (I) in refluxing toluene gives the adduct (III), which is treated first with pyrrolidine (IV) in chloroform and then with HCl in refluxing methanol to yield the pyrrolidide (V). The reduction of (V) with LiAlH4 in THF affords compound (VI), which is treated with H2 over Pd/C in THF/methanol/water to provide the aminoalcohol (VII). Finally, the amino group of (VII) is acylated by means of palmitoyl chloride (VIII) and DIEA in dichloromethane to furnish the target palmitoylamide.

参考文献中间体

【1】 Hirth, B.H.; Siegel, C. (Genzyme Corp.); Synthesis of UDP-glucose: N-Acylsphingosine glucosyltransferase inhibitors. US 2003050299; WO 0308399 .

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)	61797	2,3-dihydro-1,4-benzodioxine-6-carbaldehyde; 1,4-Benzodioxan-6-carboxaldehyde; 3,4-ethylenedioxybenzaldehyde ;benzodioxane-6-carboxaldehyde	29668-44-8	C₉H₈O₃	详情	详情
(II)	61798	(5S)-5-phenyl-2-morpholinone;5(S)-phenylmorpholin-2-one;(5S)-3,4,5,6-Tetrahydro-5-phenyl-4(H)-1,4-oxazin-2-one	144896-92-4	C₁₀H₁₁NO₂	详情	详情
(III)	61799	(1S,3S,5S)-1,3-di(2,3-dihydro-1,4-benzodioxin-6-yl)-5-phenyltetrahydro-8H-[1,3]oxazolo[4,3-c][1,4]oxazin-8-one		C₂₈H₂₅NO₇	详情	详情
(IV)	11376	Pyrrolidine	123-75-1	C₄H₉N	详情	详情
(V)	61800	(2R,3R)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-hydroxy-2-[(2-hydroxy-1-phenylethyl)amino]-1-(1-pyrrolidinyl)-1-propanone		C₂₃H₂₈N₂O₅	详情	详情
(VI)	61801	(1R,2R)-1-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-[(2-hydroxy-1-phenylethyl)amino]-3-(1-pyrrolidinyl)-1-propanol		C₂₃H₃₀N₂O₄	详情	详情
(VII)	61802	(1R,2R)-2-amino-1-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-(1-pyrrolidinyl)-1-propanol		C₁₅H₂₂N₂O₃	详情	详情
(VIII)	19273	acetyl chloride	75-36-5	C₂H₃ClO	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(2)