N'-(3-acetyl-4-hydroxyphenyl)-N,N-diethylurea -Drug Synthesis Database

【结构式】

【分子编号】33817

【品名】N'-(3-acetyl-4-hydroxyphenyl)-N,N-diethylurea

【CA登记号】

【分子式】C₁₃H₁₈N₂O₃

【分子量】250.2976

【元素组成】C 62.38% H 7.25% N 11.19% O 19.18%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(III)

The condensation of 3-acetyl-4-hydroxyaniline (I) with N,N-diethylcarbamoyl chloride (II) in pyridine gives the urea (II), which is treated with epichlorohydrin (IV) and NaOH to yield N-[3-acetyl-4-(2,3-epoxypropoxy)phenyl]-N',N'-diethylurea (V). Finally, the epoxy ring of (V) is opened with tert-butylamine (VI).

参考文献中间体

合成目标

【1】 Stormann-Menninger-Lerchenthal, H.; Pittner, H.; Zolss, G. (CL Pharma); 4-Ureido-2-acyl phenoxypropanolamine. DE 2458624; US 4034009 .

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)	33815	1-(5-amino-2-hydroxyphenyl)-1-ethanone		C₈H₉NO₂	详情	详情
(II)	33816	N,N'-Diethylcarbamoyl chloride; 1-[(chlorocarbonyl)(ethyl)amino]ethane	88-10-8	C₅H₁₀ClNO	详情	详情
(III)	33817	N'-(3-acetyl-4-hydroxyphenyl)-N,N-diethylurea		C₁₃H₁₈N₂O₃	详情	详情
(IV)	10146	Epichlorohydrin; 2-(Chloromethyl)oxirane	106-89-8	C₃H₅ClO	详情	详情
(V)	33818	N'-[3-acetyl-4-(2-oxiranylmethoxy)phenyl]-N,N-diethylurea		C₁₆H₂₂N₂O₄	详情	详情
(VI)	17895	2-Amino-2-methylpropane; tert-butylamine; 2-methyl-2-propanamine	75-64-9	C₄H₁₁N	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

There are several pathways for the preparation of the title compound according to the patent literature.

参考文献中间体

合成目标

【1】 Zoelss, G.; AT 335464 .
【2】 Koch, H.; Celiprolol hydrocloride. Drugs Fut 1979, 4, 3, 181.
【3】 Zoelss, G.; AT 335467 .
【4】 Zoelss, G.; AT 335465 .
【5】 Zoelss, G.; et al.; AT 334385 .
【6】 Celiprolol - ein kardioselektiver beta-rezeptorblocker. Chemie Linz Ag (Kurzinformation), UL/2007, (Nov. 1978) 1978.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	17895	2-Amino-2-methylpropane; tert-butylamine; 2-methyl-2-propanamine	75-64-9	C₄H₁₁N	详情	详情
(D)	24486	Diethylamine; N,N-Diethylamine	109-89-7	C₄H₁₁N	详情	详情
(B)	33816	N,N'-Diethylcarbamoyl chloride; 1-[(chlorocarbonyl)(ethyl)amino]ethane	88-10-8	C₅H₁₀ClNO	详情	详情
(I)	33818	N'-[3-acetyl-4-(2-oxiranylmethoxy)phenyl]-N,N-diethylurea		C₁₆H₂₂N₂O₄	详情	详情
(II)	33819	1-[5-amino-2-[3-(tert-butylamino)-2-hydroxypropoxy]phenyl]-1-ethanone		C₁₅H₂₄N₂O₃	详情	详情
(III)	33817	N'-(3-acetyl-4-hydroxyphenyl)-N,N-diethylurea		C₁₃H₁₈N₂O₃	详情	详情
(IV)	39491	N-[3-acetyl-4-[3-(tert-butylamino)-2-hydroxypropoxy]phenyl]urea		C₁₆H₂₅N₃O₄	详情	详情
(V)	33821	phenyl 3-acetyl-4-[3-(tert-butylamino)-2-hydroxypropoxy]phenylcarbamate		C₂₂H₂₈N₂O₅	详情	详情
(C)	31720	1-(tert-butylamino)-3-chloro-2-propanol		C₇H₁₆ClNO	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

The condensation of 4-ethoxyaniline (II) with N,N-diethylcarbamoyl chloride (II) by means of KHCO3 gives the urea (III), which is acylated with acetyl chloride and AlCl3 to yield N-(3-acetyl-4-hydroxyphenyl)-N',N'-diethylurea (IV). The alkylation of (IV) with epichlorohydrin (V) affords the adduct (VI), which is treated with HBr providing the bromoalcohol (VII). Finally this compound is treated with tert-butylamine to furnish the target urea.

参考文献中间体

合成目标

【1】 Zolss, G.; On the synthesis of the cardioselective beta-adrenergic receptor blocking agent celiprolol. Arzneim-Forsch Drug Res 1983, 33, 1a, 2.

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)	45939	4-Aminophenetole; 1-Amino-4-ethoxybenzene; 4-Aminoethoxybenzene; 4-Ethoxyphenylamine; p-Phenetidine; 4-Ethoxyaniline	156-43-4	C₈H₁₁NO	详情	详情
(II)	33816	N,N'-Diethylcarbamoyl chloride; 1-[(chlorocarbonyl)(ethyl)amino]ethane	88-10-8	C₅H₁₀ClNO	详情	详情
(III)	45940	N'-(4-ethoxyphenyl)-N,N-diethylurea		C₁₃H₂₀N₂O₂	详情	详情
(IV)	33817	N'-(3-acetyl-4-hydroxyphenyl)-N,N-diethylurea		C₁₃H₁₈N₂O₃	详情	详情
(V)	29776	1-(chloromethyl)cyclopropane	5911-08-0	C₄H₇Cl	详情	详情
(VI)	45941	N'-[3-acetyl-4-(cyclopropylmethoxy)phenyl]-N,N-diethylurea		C₁₇H₂₄N₂O₃	详情	详情
(VII)	45942	N'-[3-acetyl-4-(3-bromo-2-hydroxypropoxy)phenyl]-N,N-diethylurea		C₁₆H₂₃BrN₂O₄	详情	详情
(VIII)	17895	2-Amino-2-methylpropane; tert-butylamine; 2-methyl-2-propanamine	75-64-9	C₄H₁₁N	详情	详情

合成路线4

该中间体在本合成路线中的序号：(VI)

The reaction of D-mannitol (I) with acetone and ZnCl2 gives the diacetonide (II), which is oxidized with Pb(OAc)4 to yield the acetonide of (R)-glyceraldehyde (III). The reduction of (III) with H2 over Pd/C affords the (S)-glycerin acetonide (IV), which is treated with TsCl in pyridine to provide the corresponding tosylate (V). The condensation of (V) with the urea derivative (VI) by means of KOH in DMSO gives the adduct (VII), which is deprotected with HCl in acetone to yield the diol (VIII). Monotosylation of (VIII) with TsCl in pyridine affords the primary tosylate (IX), which is treated with Na in methanol to provide the epoxide (X). Finally this compound is treated with tert-butylamine to furnish the target (R)-enantiomer.

参考文献中间体

合成目标

【1】 Hofer, O.; Schlogl, K.; Absolute configuration and enantiomeric purity of celiprolol. Arzneim-Forsch Drug Res 1986, 36, 8, 1157.

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)	45943	(2R,3R,4R,5R)-1,2,3,4,5-heptanepentol		C₇H₁₆O₅	详情	详情
(II)	45944	(1S,2S)-1,2-bis[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-1,2-ethanediol	1707-77-3	C₁₂H₂₂O₆	详情	详情
(III)	36759	(4R)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde	15186-48-8	C₆H₁₀O₃	详情	详情
(IV)	12698	[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl]methanol	14347-78-5	C₆H₁₂O₃	详情	详情
(V)	15208	(S)-(+)-2,2-Dimethyl-4-(hydroxymethyl)-1,3-dioxolane-p-toluenesulfonate; [(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl 4-methylbenzenesulfonate	23735-43-5	C₁₃H₁₈O₅S	详情	详情
(VI)	33817	N'-(3-acetyl-4-hydroxyphenyl)-N,N-diethylurea		C₁₃H₁₈N₂O₃	详情	详情
(VII)	45945	N'-(3-acetyl-4-[[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]phenyl)-N,N-diethylurea		C₁₉H₂₈N₂O₅	详情	详情
(VIII)	45946	N'-(3-acetyl-4-[[(2R)-2,3-dihydroxypropyl]oxy]phenyl)-N,N-diethylurea		C₁₆H₂₄N₂O₅	详情	详情
(IX)	45947	(2S)-3-(2-acetyl-4-[[(diethylamino)carbonyl]amino]phenoxy)-2-hydroxypropyl 4-methylbenzenesulfonate		C₂₃H₃₀N₂O₇S	详情	详情
(X)	45948	N'-[3-acetyl-4-[(2R)oxiranylmethoxy]phenyl]-N,N-diethylurea		C₁₆H₂₂N₂O₄	详情	详情
(XI)	17895	2-Amino-2-methylpropane; tert-butylamine; 2-methyl-2-propanamine	75-64-9	C₄H₁₁N	详情	详情

Extended Information