N,N'-Diethylcarbamoyl chloride; 1-[(chlorocarbonyl)(ethyl)amino]ethane -Drug Synthesis Database

【结构式】

【分子编号】33816

【品名】N,N'-Diethylcarbamoyl chloride; 1-[(chlorocarbonyl)(ethyl)amino]ethane

【CA登记号】88-10-8

【分子式】C₅H₁₀ClNO

【分子量】135.59324

【元素组成】C 44.29% H 7.43% Cl 26.15% N 10.33% O 11.8%

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：(II)

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：(B)

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：(II)

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：(IX)

The reaction of 4-nitrophenol (I) with acetic anhydride in aqueous NaOH gives the corresponding acetate (II), which is submitted to a Fries migration with AlCl3 in nitrobenzene at 140 C to yield the acetophenone (III). The condensation of (III) with epichlorohydrin (IV) by means of K2CO3 affords the adduct (V), which is treated with tert-butylamine (VI) in water to obtain the aminoisopropanol derivative (VII). The reduction of the nitro group of (VII) with H2 over Pd/C in methanol gives the corresponding amino derivative (VIII), which is finally condensed with N,N-diethylcarbamoyl chloride (IX) by means of TEA in THF to yield the target urea.

参考文献中间体

合成目标

【1】 Joshi, R.A.; et al.; A new and improved process for celiprolol hydrochloride. Org Process Res Dev 2001, 5, 2, 176.

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)	11236	4-Nitrophenol; p-Nitrophenol	100-02-7	C₆H₅NO₃	详情	详情
(II)	50841	4-Nitrophenyl acetate; Acetic acid 4-nitrophenyl ester; p-Nitrophenyl acetate	830-03-5	C₈H₇NO₄	详情	详情
(III)	50842	1-(2-hydroxy-5-nitrophenyl)-1-ethanone		C₈H₇NO₄	详情	详情
(IV)	10146	Epichlorohydrin; 2-(Chloromethyl)oxirane	106-89-8	C₃H₅ClO	详情	详情
(V)	50843	1-[5-nitro-2-(2-oxiranylmethoxy)phenyl]-1-ethanone		C₁₁H₁₁NO₅	详情	详情
(VI)	17895	2-Amino-2-methylpropane; tert-butylamine; 2-methyl-2-propanamine	75-64-9	C₄H₁₁N	详情	详情
(VII)	50844	1-[2-[3-(tert-butylamino)-2-hydroxypropoxy]-5-nitrophenyl]-1-ethanone		C₁₅H₂₂N₂O₅	详情	详情
(VIII)	33819	1-[5-amino-2-[3-(tert-butylamino)-2-hydroxypropoxy]phenyl]-1-ethanone		C₁₅H₂₄N₂O₃	详情	详情
(IX)	33816	N,N'-Diethylcarbamoyl chloride; 1-[(chlorocarbonyl)(ethyl)amino]ethane	88-10-8	C₅H₁₀ClNO	详情	详情

Extended Information