【结 构 式】 |
【分子编号】33819 【品名】1-[5-amino-2-[3-(tert-butylamino)-2-hydroxypropoxy]phenyl]-1-ethanone 【CA登记号】 |
【 分 子 式 】C15H24N2O3 【 分 子 量 】280.36724 【元素组成】C 64.26% H 8.63% N 9.99% O 17.12% |
合成路线1
该中间体在本合成路线中的序号:(VII)The reaction of 3-acetyl-4-[3-(tert-butylamino)-2-hydroxypropoxy)aniline (VII) with phenyl carbamate (VIII) in pyridine gives the N-[3-acetyl-4-[3-(tert-butylamino)-2-hydroxypropoxy]phenylcarbamic acid phenyl ester (IX), which is tretated with diethylamine (X) in ethanol/water. By reaction of N-[3-acetyl-4-(3-chloro-2-hydroxypropoxy)phenyl]-N',N'-diethylurea (XI) with tert-butylamine (VI).
【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 |
---|---|---|---|---|---|---|
(VI) | 17895 | 2-Amino-2-methylpropane; tert-butylamine; 2-methyl-2-propanamine | 75-64-9 | C4H11N | 详情 | 详情 |
(VII) | 33819 | 1-[5-amino-2-[3-(tert-butylamino)-2-hydroxypropoxy]phenyl]-1-ethanone | C15H24N2O3 | 详情 | 详情 | |
(VIII) | 33820 | phenyl carbamate | 622-46-8 | C7H7NO2 | 详情 | 详情 |
(IX) | 33821 | phenyl 3-acetyl-4-[3-(tert-butylamino)-2-hydroxypropoxy]phenylcarbamate | C22H28N2O5 | 详情 | 详情 | |
(X) | 24486 | Diethylamine; N,N-Diethylamine | 109-89-7 | C4H11N | 详情 | 详情 |
(XI) | 33822 | N'-[3-acetyl-4-(3-chloro-2-hydroxypropoxy)phenyl]-N,N-diethylurea | C16H23ClN2O4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(II)There are several pathways for the preparation of the title compound according to the patent literature.
【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:(VIII)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.
【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 |