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【结 构 式】 
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【分子编号】31720 【品名】1-(tert-butylamino)-3-chloro-2-propanol 【CA登记号】 |
【 分 子 式 】C7H16ClNO 【 分 子 量 】165.66288 【元素组成】C 50.75% H 9.73% Cl 21.4% N 8.45% O 9.66% |
合成路线1
该中间体在本合成路线中的序号：(III)It can be prepared in two different ways: 1) The reaction of 1-chloro-2,3-propylene oxide (I) with tert-butylamine (II) in ether yields 1-chloro-3-tert-butylamino-2-propanol (III), which is condensed with 2,3-xylenol (IV) by means of KOH in ether-water. 2) By heating a mixture of 1-tert-butyl-3-azetidinol (V) and 2,3-xylenol (IV) at 155 C with KOH.
| 【1】 Suzuki, Y.; et al.; JP 45029294 . |
| 【2】 Tsukamoto, K.; et al.; JP 46028534 . |
| 【3】 Castaner, J.; Weetman, D.F.; D-32. Drugs Fut 1977, 2, 2, 91. |
| 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) | 10146 | Epichlorohydrin; 2-(Chloromethyl)oxirane | 106-89-8 | C3H5ClO | 详情 | 详情 |
| (II) | 17895 | 2-Amino-2-methylpropane; tert-butylamine; 2-methyl-2-propanamine | 75-64-9 | C4H11N | 详情 | 详情 |
| (III) | 31720 | 1-(tert-butylamino)-3-chloro-2-propanol | C7H16ClNO | 详情 | 详情 | |
| (IV) | 40074 | 2,3-dimethylphenol | 526-75-0 | C8H10O | 详情 | 详情 |
| (V) | 40075 | 1-(tert-butyl)-3-azetidinol | 13156-04-2 | C7H15NO | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)The reaction of 5-fluorosalicylaldehyde (I) with 1-chloro-3-(tert-butylamino)-2-propanol (II) by means of p-toluenesulfonic acid in refluxing benzene gives 5-chloromethyl-3-(tert-butyl)-2-(2-hydroxy-5-fluorophenyl)oxazolidine (III), which is cyclized again by treatment with NaH in hot DMF to afford 8-aza-4,9-dioxa-11-fluoro-8-(tert-butyl)-2,3-benzobicyclo[4.2.1]octan (IV). Hydrolysis of (IV) with aqueous 1N HCl at 80 C yields 1-(2-formyl-4-fluorophenoxy)-3-(tert-butylamino)-2-propanol (V), which is submitted to a Grignard reaction with propylmagnesium bromide (A) in refluxing ether to afford 1-[2-(1-hydroxybutyl)-4-fluorophenoxy]-3-(tert-butylamino)-2-propanol (VI). Finally, this compound is oxidized with chromic acid in acetone - H2SO4.
| 【1】 Demarne le Florence, H.; Compositions for treatment of cardiovascular conditions associated with overproduction of catecholamines. BE 0830766; CA 1052820; DE 2528147; FR 2276032; GB 1501632; JP 51023233; NL 7507703; US 4252825; US 4302601 . |
| 【2】 Castaner, J.; Blancafort, P.; Serradell, M.N.; Neuman, M.; Butofilolol. Drugs Fut 1982, 7, 2, 96. |
| 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) | 10970 | (4R)-4-[3-(Benzyloxy)-4-methoxyphenyl]-2-pyrrolidinone | C18H19NO3 | 详情 | 详情 | |
| (I) | 31719 | 5-fluoro-2-hydroxybenzaldehyde | C7H5FO2 | 详情 | 详情 | |
| (II) | 31720 | 1-(tert-butylamino)-3-chloro-2-propanol | C7H16ClNO | 详情 | 详情 | |
| (III) | 31721 | 2-[3-(tert-butyl)-5-(chloromethyl)-1,3-oxazolidin-2-yl]-4-fluorophenol | C14H19ClFNO2 | 详情 | 详情 | |
| (IV) | 31722 | 11-(tert-butyl)-4-fluoro-8,12-dioxa-11-azatricyclo[7.2.1.0(2,7)]dodeca-2,4,6-triene | C13H16FNO2 | 详情 | 详情 | |
| (V) | 31723 | 2-[3-(tert-butylamino)-2-hydroxypropoxy]-5-fluorobenzaldehyde | C14H20FNO3 | 详情 | 详情 | |
| (VI) | 31724 | 1-[2-[3-(tert-butylamino)-2-hydroxypropoxy]-5-fluorophenyl]-1-butanol | C17H28FNO3 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(C)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4
该中间体在本合成路线中的序号：(C)Compound can be prepared in three different ways: 1) Condensation of 2,5-dichlorophenol (I) with epichlorohydrin (A) by means of NaOH in water to give 1-(2,5-dichlorophenoxy)-2,3-epoxypropane (II), which is then condensed again with tert-butylamine in refluxing ethanol. Finally, HCl in ethanol is added. 2) Condensation of (I) with epichlorohydrin (A) by means of pyridine gives 1-(2,5-dichlorophenoxy)-3-chloro-2-propanol (III), which is then condensed with tert-butylamine as before. 3) Condensation of (I) with 1-(tertbutylamino)-2,3-epoxypropane (B) or with 1-(tertbutylamino)-3-chloro-2-propanol (C) by means of NaOH in refluxing ethanol.
| 【1】 Hajos, A.; et al.; Aminopropanol derivative. DE 2213044; FR 2130284; GB 1337921; NL 7203323 . |
| 【2】 Castaner, J.; Sumgurbey, K.; GYKI-41099. Drugs Fut 1978, 3, 4, 295. |
| 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) | 10146 | Epichlorohydrin; 2-(Chloromethyl)oxirane | 106-89-8 | C3H5ClO | 详情 | 详情 |
| (B) | 33503 | N-(tert-butyl)-N-(2-oxiranylmethyl)amine; 2-methyl-N-(2-oxiranylmethyl)-2-propanamine | C7H15NO | 详情 | 详情 | |
| (I) | 11953 | 2,5-Dichlorophenol | 583-78-8 | C6H4Cl2O | 详情 | 详情 |
| (II) | 33501 | 2,5-dichlorophenyl 2-oxiranylmethyl ether; 2-[(2,5-dichlorophenoxy)methyl]oxirane | C9H8Cl2O2 | 详情 | 详情 | |
| (III) | 33502 | 1-chloro-3-(2,5-dichlorophenoxy)-2-propanol | C9H9Cl3O2 | 详情 | 详情 | |
| (C) | 31720 | 1-(tert-butylamino)-3-chloro-2-propanol | C7H16ClNO | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(V)The reaction of 5-carboxy-2-acetylthiophene (I) first with SOCl2 in refluxing toluene, and then with aqueous ammonia gives 5-carbamoyl-2-acetylthiophene (II), which is brominated with Br2 in hot acetic acid yielding 5-carbamoyl-2-bromoacetylthiophene (III). The cyclization of (III) with ammonium dithiocarbamate (A) in refluxing methanol-DMF affords 2-mercapto-4-(5'-carbamoyl-2'-thienyl)thiazole (IV), which is finally condensed with 1-chloro-3-tert-butylaminoisopropanol (V) by means of NaOH in water methanol.
| 【1】 Hara, Y.; et al.; Synthesis and beta-adrenergic blocking action of a new thiazolylthiopropanolamine derivative. J Pharm Sci 1978, 67, 1334-35. |
| 【2】 Hibino, T.; et al.; JP 7525562 . |
| 【3】 Hibino, T.; et al.; JP 7576069 . |
| 【4】 Hibino, T.; et al. (Sumitomo Chemical Co., Ltd.); Thiazole derivatives. DE 2341753; FR 2196162; GB 1435139; NL 7311248; US 3932400 . |
| 【5】 Reiner, A. (SkyePharma AG); Process for preparing ursodeoxycholic acid derivates and their inorganic and organic salts having therapeutic activity. EP 0272462 . |
| 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) | 33253 | ammonium carbamodithioate | CH6N2S2 | 详情 | 详情 | |
| (I) | 33250 | 5-acetyl-2-thiophenecarboxylic acid | 4066-41-5 | C7H6O3S | 详情 | 详情 |
| (II) | 33251 | 5-acetyl-2-thiophenecarboxamide | C7H7NO2S | 详情 | 详情 | |
| (III) | 33252 | 5-(2-bromoacetyl)-2-thiophenecarboxamide | C7H6BrNO2S | 详情 | 详情 | |
| (IV) | 33254 | 5-(2-sulfanyl-1,3-thiazol-4-yl)-2-thiophenecarboxamide | C8H6N2OS3 | 详情 | 详情 | |
| (V) | 31720 | 1-(tert-butylamino)-3-chloro-2-propanol | C7H16ClNO | 详情 | 详情 |