N-(1,3-benzothiazol-2-yl)-N-phenylamine; N-phenyl-1,3-benzothiazol-2-amine -Drug Synthesis Database

【结构式】

【分子编号】46364

【品名】N-(1,3-benzothiazol-2-yl)-N-phenylamine; N-phenyl-1,3-benzothiazol-2-amine

【CA登记号】

【分子式】C₁₃H₁₀N₂S

【分子量】226.30188

【元素组成】C 69% H 4.45% N 12.38% S 14.17%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XII)

In an alternative procedure, 2-aminothiophenol (X) was condensed with phenyl isothiocyanate (XII) to produce N-phenyl-2-aminobenzothiazole (XIII). Subsequent Friedel-Crafts acylation of (XIII) with acid chloride (II) gave chloro ketone (XIV), which was converted to amino ketone (XV) upon treatment with dimethylamine. After ketone (XV) reduction with NaBH4, the resulting amino alcohol (XVI) was treated with carbonyl diimidazole, and the mixture of isomers was chromatographically separated as above.

参考文献中间体

合成目标

【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.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XVIa)	46367	(1R,2S)-1-[4-(1,3-benzothiazol-2-ylamino)phenyl]-2-(dimethylamino)-1-propanol		C₁₈H₂₁N₃OS	详情	详情
(XVIb)	46368	(1S,2S)-1-[4-(1,3-benzothiazol-2-ylamino)phenyl]-2-(dimethylamino)-1-propanol		C₁₈H₂₁N₃OS	详情	详情
(X)	25182	2-aminobenzenethiol	137-07-5	C₆H₇NS	详情	详情
(XI)	46363	benzenesulfenyl cyanide		C₇H₅NS	详情	详情
(XII)	46364	N-(1,3-benzothiazol-2-yl)-N-phenylamine; N-phenyl-1,3-benzothiazol-2-amine		C₁₃H₁₀N₂S	详情	详情
(XIII)	12926	2-Chloropropanoyl chloride; 2-Chloropropionyl chloride	7623-09-8	C₃H₄Cl₂O	详情	详情
(XIV)	46365	1-[4-(1,3-benzothiazol-2-ylamino)phenyl]-2-chloro-1-propanone		C₁₆H₁₃ClN₂OS	详情	详情
(XV)	46366	1-[4-(1,3-benzothiazol-2-ylamino)phenyl]-2-(dimethylamino)-1-propanone		C₁₈H₁₉N₃OS	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 cyclization of 1,3-diphenylthiourea (I) with Br2 and HBr in water gives N-(benzothiazol-2-yl)-N-phenylamine (II), which is condensed with 2-chloropropionyl chloride (III) by means of AlCl3 in dichloromethane to yield the propiophenone (IV). The reaction of (IV) with dimethylamine in isopropanol affords the racemic alpha-(dimethylamino) propiophenone (V), which is optically resolved by means of (+)(D)-di-p-toluoyltartaric acid providing the (S)-enantiomer (VI) with a 80% ee. The reduction of (VI) with NaBH4 and NaOH in isopropanol gives the (S,S)-enantiomer (VII) with a 85% ee. Finally, this compound is condensed with CDI and imidazole to afford the target compound that is purified by crystallization in ethyl acetate up to a 99% ee.

参考文献中间体

合成目标

【1】 Aelterman, W.; et al.; Conversion of the laboratory synthetic route of the N-aryl-2-benzothiazolamine R116010 to a manufacturing method. Org Process Res Dev 2001, 5, 5, 467.

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)	56953	1,3-Diphenyl-2-thiourea; 1,3-Diphenylthiourea; N,N'-Diphenylthiourea; S-Diphenylthiocarbamide; sym-Diphenylthiourea; Thiocarbanilide	102-08-9	C₁₃H₁₂N₂S	详情	详情
(II)	46364	N-(1,3-benzothiazol-2-yl)-N-phenylamine; N-phenyl-1,3-benzothiazol-2-amine		C₁₃H₁₀N₂S	详情	详情
(III)	12926	2-Chloropropanoyl chloride; 2-Chloropropionyl chloride	7623-09-8	C₃H₄Cl₂O	详情	详情
(IV)	46365	1-[4-(1,3-benzothiazol-2-ylamino)phenyl]-2-chloro-1-propanone		C₁₆H₁₃ClN₂OS	详情	详情
(V)	46366	1-[4-(1,3-benzothiazol-2-ylamino)phenyl]-2-(dimethylamino)-1-propanone		C₁₈H₁₉N₃OS	详情	详情
(VI)	56954	(2S)-1-[4-(1,3-benzothiazol-2-ylamino)phenyl]-2-(dimethylamino)-1-propanone		C₁₈H₁₉N₃OS	详情	详情
(VII)	46368	(1S,2S)-1-[4-(1,3-benzothiazol-2-ylamino)phenyl]-2-(dimethylamino)-1-propanol		C₁₈H₂₁N₃OS	详情	详情

Extended Information