【结 构 式】 |
【分子编号】61065 【品名】2-bromo-4-(2-chlorophenyl)-9-cyclohexyl-5,6-dihydro-4H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine 【CA登记号】 |
【 分 子 式 】C20H20BrClN4S 【 分 子 量 】463.82846 【元素组成】C 51.79% H 4.35% Br 17.23% Cl 7.64% N 12.08% S 6.91% |
合成路线1
该中间体在本合成路线中的序号:(IX)The reduction of 2-chloroacetylamino-3-(o-chlorobenzoyl)thiophene (I) with NaBH4 in DMF gives 2-chloroacetylamino-3-[(o-chlorophenyl)hydroxymethyl]thiophene (II), which is cyclized by means of sodium isopropoxide in refluxing isopropanol to afford 5-(o-chlorophenyl)thieno[2,3-e]-4,1-oxazepin-2-one (III). The bromination of (III) with Br2 in CHCl3 - pyridine yields 7-bromo-5-(o-chlorophenyl)thieno[2,3-e]-4,1-oxazepin-2-one (IV), which by reaction with P2S5 and NaHCO3 in hot diglyme is converted into 7-bromo-5-(o-chlorophenyl)thieno[2,3-e]-4,1-oxazepin-2-thione (V) (1). The cyclization of (V) with cyclohexanecarboxyl hydrazide (A) in THF gives 7-bromo-5-(o-chlorophenyl)-1-cyclohexylthieno[2,3-e]triazolo[3,4-c]-4,1-oxazepin-2-one (VI). The ring opening of (VI) by treatment with concentrated HBr yields 3-cyclohexyl-4-[3-(o-chlorophenylbromomethyl)-5-bromo-2-thienyl]-5-hydroxymethyl-1,2,4-triazole (VII), which by reaction with SOCl2 is converted into 3-cyclohexyl-4-[3-(o-chlorophenyl-bromomethyl)-5-bromo-2-thienyl]-5-chloromethyl-1,2,4-triazole (VIII). The cyclization of (VIII) with NH3 in methanol a 100 C in a pressure vessel yields 8-bromo-6-(o-chlorophenyl)-1-cyclohexyl-4H-s-triazolo[3,4-c]thieno[2,3-e]-5,6-dihydro-1,4-diazepine (IX), which is finally dehydrogenated by treatment with KMnO4 in refluxing acetone
【1】 Weber, K.H.; et al. (C.H. Boehringer Sohn); BE 844170; CA 1077475; DD 126744; DE 2531677; DE 2531678; DE 2531679; DE 2533924; FR 2318165; GB 1550679; GB 1550680; JP 7712189; JP 7712193; JP 7714800; JP 7717496; NL 7607871; NL 7607872; US 4201712; ZA 7604212 . |
【2】 Blancafort, P.; Serradell, M.N.; Castaner, J.; Owen, R.T.; Ciclotizolam. Drugs Fut 1981, 6, 6, 342. |
【3】 Imvamune IND receives approval. Justus Liebigs Ann Chem. 1978, 1257. |
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) | 61061 | cyclohexanecarbohydrazide | C7H14N2O | 详情 | 详情 | |
(I) | 61056 | 2-chloro-N-[3-(2-chlorobenzoyl)-2-thienyl]acetamide | C13H9Cl2NO2S | 详情 | 详情 | |
(II) | 61057 | 2-chloro-N-{3-[(2-chlorophenyl)(hydroxy)methyl]-2-thienyl}acetamide | C13H11Cl2NO2S | 详情 | 详情 | |
(III) | 61058 | 5-(2-chlorophenyl)-1,5-dihydrothieno[2,3-e][1,4]oxazepin-2(3H)-one | C13H10ClNO2S | 详情 | 详情 | |
(IV) | 61059 | 7-bromo-5-(2-chlorophenyl)-1,5-dihydrothieno[2,3-e][1,4]oxazepin-2(3H)-one | C13H9BrClNO2S | 详情 | 详情 | |
(V) | 60160 | (3S,8R,9S,10R,13S,14S,16S,17S)-3-{[tert-butyl(dimethyl)silyl]oxy}-17-[(1S)-1-(2-isopentyl-1,3-dioxolan-2-yl)ethyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-16,17-diol | C35H62O5Si | 详情 | 详情 | |
(VI) | 61062 | 2-bromo-4-(2-chlorophenyl)-9-cyclohexyl-4H,6H-thieno[2,3-e][1,2,4]triazolo[3,4-c][1,4]oxazepine | C20H19BrClN3OS | 详情 | 详情 | |
(VII) | 60163 | 4-fluorobenzaldehyde | C7H5FO | 详情 | 详情 | |
(VIII) | 61064 | 4-{5-bromo-3-[bromo(2-chlorophenyl)methyl]-2-thienyl}-3-(chloromethyl)-5-cyclohexyl-4H-1,2,4-triazole | C20H19Br2Cl2N3S | 详情 | 详情 | |
(IX) | 61065 | 2-bromo-4-(2-chlorophenyl)-9-cyclohexyl-5,6-dihydro-4H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine | C20H20BrClN4S | 详情 | 详情 |