2-hydroxy-N-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]acetamide -Drug Synthesis Database

【结构式】

【分子编号】29857

【品名】2-hydroxy-N-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]acetamide

【CA登记号】

【分子式】C₁₇H₂₆N₂O₃

【分子量】306.40512

【元素组成】C 66.64% H 8.55% N 9.14% O 15.66%

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：(VIII)

The reductocondensation of piperidine (I) with 3-hydroxybenzaldehyde (II) by means of sodium borohydride in ethanol gives 3-(1-piperidylmethyl)phenol (III), which is then condensed with N-(3-bromopropyl)phthalimide (IV) by means of NaH in DMF yielding N-[3-[3-(1-piperidylmethyl)phenoxy]propyl]phthalimide (V). The hydrolysis of (V) with hydrazine in ethanol affords 3-[3-(1-piperidylmethyl)phenoxy]propylamine (VI), which is acylated with hydroxyacetic acid (VII) at 200 C giving N-[3-[3-(1-piperidylmethyl)phenoxy]propyl]hydroxyacetamide (VIII). Finally, this compound is acetylated with acetic anhydride at 100 C.

参考文献中间体

合成目标

【1】 Shibata, K.; et al. (Teikoku Hormone Manufacturing Co., Ltd.); Antiulcer phenoxypropylamine derivatives. EP 0024510; JP 81115750; US 4293557 .
【2】 Castaner, J.; Serradell, M.N.; TZU-0460. Drugs Fut 1985, 10, 12, 995.

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)	10158	Piperidine	110-89-4	C₅H₁₁N	详情	详情
(II)	28537	3-hydroxybenzaldehyde	100-83-4	C₇H₆O₂	详情	详情
(III)	29854	3-(1-piperidinylmethyl)phenol		C₁₂H₁₇NO	详情	详情
(IV)	15216	N-(3-Bromopropyl)phthalimide; 2-(3-bromopropyl)-1H-isoindole-1,3(2H)-dione	5460-29-7	C₁₁H₁₀BrNO₂	详情	详情
(V)	29855	2-[2-[3-(1-piperidinylmethyl)phenoxy]ethyl]-1H-isoindole-1,3(2H)-dione		C₂₂H₂₄N₂O₃	详情	详情
(VI)	16105	3-[3-(piperidinomethyl)phenoxy]-1-propanamine; 3-[3-(piperidinomethyl)phenoxy]propylamine		C₁₅H₂₄N₂O	详情	详情
(VII)	29856	2-hydroxyacetic acid;glycolic acid	79-14-1	C₂H₄O₃	详情	详情
(VIII)	29857	2-hydroxy-N-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]acetamide		C₁₇H₂₆N₂O₃	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 alkylation of 3-hydroxybenzaldehyde (I) with N-(3-bromopropyl)phthalimide (II) in the presence of NaOMe leads to 3-(phthalimidopropoxy)benzaldehyde (III). The reductive alkylation of piperidine with aldehyde (III) in the presence of formic acid gives N-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]phthalimide (IV), which is converted to N-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]amine (V) by treatment with 6N HCl. Condensation of (V) with glycolic acid in boiling xylene provides N-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]-2-hydroxyacetamide (VI), which is complexed with bismuth (+3) citrate (VII) in boiling water.

参考文献中间体

合成目标

【1】 Petkov, O.; Lytakov, G.; Taskov, M.; Savov, E.; Kostev, V.; Tsvetkova, E.; Nikolov, G.; Atanassova, R.; Ivanov, C.; Synthesis, gastroprotective, antisecretory and anti-Helicobacter effect of +[3(3-(1-piperidinylmethyl)phenoxy)propyl]hydroxyacetamide-2-hydroxypropane-1,2,3-tricarboxylate-bismuth(3+) complex (MX1). J Pharm Pharmacol 1996, 3, 3, 297-301.
【2】 N-(3-(3-(1-Piperidinylmethyl)phenoxy)propyl)propenetricarboxylate bismuth (3+) complex and the method for preparation. WO 9509162 .
【3】 Mondeshka, D.; Spassov, G.; Krushkov, I.; Ivanov, C.; Marazova, K.; Roxatidine Bismuth Citrate. Drugs Fut 2000, 25, 5, 462.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10158	Piperidine	110-89-4	C₅H₁₁N	详情	详情
(I)	28537	3-hydroxybenzaldehyde	100-83-4	C₇H₆O₂	详情	详情
(II)	15216	N-(3-Bromopropyl)phthalimide; 2-(3-bromopropyl)-1H-isoindole-1,3(2H)-dione	5460-29-7	C₁₁H₁₀BrNO₂	详情	详情
(III)	35289	3-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propoxy]benzaldehyde		C₁₈H₁₅NO₄	详情	详情
(IV)	35290	2-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]-1H-isoindole-1,3(2H)-dione		C₂₃H₂₆N₂O₃	详情	详情
(V)	16105	3-[3-(piperidinomethyl)phenoxy]-1-propanamine; 3-[3-(piperidinomethyl)phenoxy]propylamine		C₁₅H₂₄N₂O	详情	详情
(VI)	29857	2-hydroxy-N-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]acetamide		C₁₇H₂₆N₂O₃	详情	详情
(VII)	13855	bismuth(3+) 2-hydroxy-1,2,3-propanetricarboxylate; Bismuth Citrate	813-93-4	C₆H₅BiO₇	详情	详情

Extended Information