【结 构 式】 |
【分子编号】46352 【品名】N-[4-[(1S,2S)-2-(dimethylamino)-1-hydroxypropyl]phenyl]acetamide 【CA登记号】 |
【 分 子 式 】C13H20N2O2 【 分 子 量 】236.31408 【元素组成】C 66.07% H 8.53% N 11.85% O 13.54% |
合成路线1
该中间体在本合成路线中的序号:(Vb)Friedel-Crafts acylation of acetanilide (I) with 2-chloropropionyl chloride (II) in the presence of AlCl3 provided ketone (III). The chlorine atom of (III) was then displaced with dimethylamine to afford amino ketone (IV), which was reduced to alcohol (V) using NaBH4 in MeOH. Treatment of alcohol (V) with carbonyl diimidazole furnished the imidazolyl derivative (VI). The acetamido group of (VI) was then hydrolyzed with 3N HCl to give aniline (VII). This compound was converted to isothiocyanate (VIII) by treatment with thiophosgene and NaOH. Alternatively, aniline (VII) was treated with carbon disulfide and NaOH and then with iodomethane to give the bis(methylthio)methyleneamino derivative (IX). The condensation of either (VIII) or (IX) with 2-aminothiophenol (X) produced the target benzothiazole (XI) as a mixture of isomers. Then, separation of the diastereoisomers by column chromatography, followed by resolution by chiral HPLC, furnished the title (S,S)-isomer.
【1】 Venet, M.; Van Wauwe, J.; Mabire, D.; Sanz, G.; Poignet, H.; Wouters, J.; Synthesis of R116010, a retinoic acid (RA) metabolism inhibitor with antitumoral effects. 16th Int Symp Med Chem (Sept 18 2000, Bologna) 2000, Abst PC-60. |
【2】 Venet, M.G.; Mabire, D.J.-P.; Lacrampe, J.F.A.; Sanz, G.C. (Janssen Pharmaceutica NV); N-[4-(heteroarylmethyl)phenyl]-heteroarylamines. EP 0907650; JP 2000503670; US 6124330; WO 9749704 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(Va) | 46351 | N-[4-[(1R,2S)-2-(dimethylamino)-1-hydroxypropyl]phenyl]acetamide | C13H20N2O2 | 详情 | 详情 | |
(Vb) | 46352 | N-[4-[(1S,2S)-2-(dimethylamino)-1-hydroxypropyl]phenyl]acetamide | C13H20N2O2 | 详情 | 详情 | |
(VIa) | 46353 | N-[4-[(1R,2S)-2-(dimethylamino)-1-(1H-imidazol-1-yl)propyl]phenyl]acetamide | C16H22N4O | 详情 | 详情 | |
(VIb) | 46354 | N-[4-[(1S,2S)-2-(dimethylamino)-1-(1H-imidazol-1-yl)propyl]phenyl]acetamide | C16H22N4O | 详情 | 详情 | |
(VIIa) | 46355 | N-[(1S,2R)-2-(4-aminophenyl)-2-(1H-imidazol-1-yl)-1-methylethyl]-N,N-dimethylamine; 4-[(1R,2S)-2-(dimethylamino)-1-(1H-imidazol-1-yl)propyl]aniline | C14H20N4 | 详情 | 详情 | |
(VIIb) | 46356 | N-[(1S,2S)-2-(4-aminophenyl)-2-(1H-imidazol-1-yl)-1-methylethyl]-N,N-dimethylamine; 4-[(1S,2S)-2-(dimethylamino)-1-(1H-imidazol-1-yl)propyl]aniline | C14H20N4 | 详情 | 详情 | |
(VIIIa) | 46357 | (1R,2S)-1-(1H-imidazol-1-yl)-1-(4-isothiocyanatophenyl)-N,N-dimethyl-2-propanamine; N-[(1S,2R)-2-(1H-imidazol-1-yl)-2-(4-isothiocyanatophenyl)-1-methylethyl]-N,N-dimethylamine | C15H18N4S | 详情 | 详情 | |
(VIIIb) | 46358 | N-[(1S,2S)-2-(1H-imidazol-1-yl)-2-(4-isothiocyanatophenyl)-1-methylethyl]-N,N-dimethylamine; (1S,2S)-1-(1H-imidazol-1-yl)-1-(4-isothiocyanatophenyl)-N,N-dimethyl-2-propanamine | C15H18N4S | 详情 | 详情 | |
(IXa) | 46359 | 1-[(1R,2S)-1-(4-[[bis(methylsulfanyl)methylene]amino]phenyl)-2-(dimethylamino)propyl]-1H-imidazole | C17H24N4S2 | 详情 | 详情 | |
(IXb) | 46360 | 1-[(1S,2S)-1-(4-[[bis(methylsulfanyl)methylene]amino]phenyl)-2-(dimethylamino)propyl]-1H-imidazole | C17H24N4S2 | 详情 | 详情 | |
(XIa) | 46361 | N-[4-[(1R,2S)-2-(dimethylamino)-1-(1H-imidazol-1-yl)propyl]phenyl]-1,3-benzothiazol-2-amine; N-(1,3-benzothiazol-2-yl)-N-[4-[(1R,2S)-2-(dimethylamino)-1-(1H-imidazol-1-yl)propyl]phenyl]amine | C21H23N5S | 详情 | 详情 | |
(XIb) | 46362 | N-[4-[(1S,2S)-2-(dimethylamino)-1-(1H-imidazol-1-yl)propyl]phenyl]-1,3-benzothiazol-2-amine; N-(1,3-benzothiazol-2-yl)-N-[4-[(1S,2S)-2-(dimethylamino)-1-(1H-imidazol-1-yl)propyl]phenyl]amine | C21H23N5S | 详情 | 详情 | |
(I) | 10194 | N-Phenylacetamide; Acetanilide | 103-84-4 | C8H9NO | 详情 | 详情 |
(II) | 12926 | 2-Chloropropanoyl chloride; 2-Chloropropionyl chloride | 7623-09-8 | C3H4Cl2O | 详情 | 详情 |
(III) | 46349 | N-[4-(2-chloropropanoyl)phenyl]acetamide | C11H12ClNO2 | 详情 | 详情 | |
(IV) | 46350 | N-[4-[2-(dimethylamino)propanoyl]phenyl]acetamide | C13H18N2O2 | 详情 | 详情 | |
(X) | 25182 | 2-aminobenzenethiol | 137-07-5 | C6H7NS | 详情 | 详情 |