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【结 构 式】 
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【分子编号】39503 【品名】6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b][1,3]thiazole 【CA登记号】 |
【 分 子 式 】C11H12N2S 【 分 子 量 】204.29576 【元素组成】C 64.67% H 5.92% N 13.71% S 15.7% |
合成路线1
该中间体在本合成路线中的序号：(rac)-(XII)The reaction of beta-chloroethylamine (III) with ammonium thiocyanate (B) gives beta-aminoethylthiocyanate (IV), which is alkylated with alpha,beta-dichloroethylbenzene (V) in hot benzene yielding the secondary amine (VI). The cyclization of (VI) in hot aqueous NaOH affords racemic levamisole, which is finally resolved in its optical isomers through the d-10-camphorsulfonate or N-benzene (or p-toluene)sulfonyl-L-(+)-glutamic salt.
| 【1】 Bullock, M.W.; DE 1645975 . |
| 【2】 Dick, P.R.; Rombi, M.; FR 2183313 . |
| 【3】 Castañer, J.; Hopkins, S.J.; Blancafort, P.; Serradell, M.N.; Levamisole hydrochloride. Drugs Fut 1979, 4, 6, 420. |
| 【4】 US 3579530 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (B) | 39499 | ammonium thiocyanate | 1762-95-4 | CH4N2S | 详情 | 详情 |
| (rac)-(XII) | 39503 | 6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b][1,3]thiazole | C11H12N2S | 详情 | 详情 | |
| (III) | 33455 | 2-chloro-1-ethanamine; 2-chloroethylamine | C2H6ClN | 详情 | 详情 | |
| (IV) | 39500 | 2-amino-1-ethanesulfenyl cyanide | C3H6N2S | 详情 | 详情 | |
| (V) | 39501 | 1-(1,2-dichloroethyl)benzene | 1074-11-9 | C8H8Cl2 | 详情 | 详情 |
| (VI) | 39502 | 2-[(2-chloro-2-phenylethyl)amino]-1-ethanesulfenyl cyanide | C11H13ClN2S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(rac)-(XII)The reaction of phenacyl bromide (VII) with 2-aminothiazoline (VIII) in MeCN at 100 C gives 2-imino-3-phenacylthiazolidine (IX), which is reduced to the corresponding alcohol (X) with NaBH4 in methanol. Finally, this compound is cyclized with SOCl2 and refluxing acetic anhydride giving the racemic levamisole which is resolved resolved in its optical isomers through the d-10-camphorsulfonate, N-benzene (or p-toluene)sulfonyl-L-(+)-glutamic salt. Compound (X) can be acetylated under milder conditions than before giving the N-acetyl compound (XI), which is cyclized SOCl2 and refluxing acetic anhydride.
| 【1】 Janssen Pharm. N.V.; US 3274209 . |
| 【2】 US 3579530 . |
| 【3】 Castañer, J.; Hopkins, S.J.; Blancafort, P.; Serradell, M.N.; Levamisole hydrochloride. Drugs Fut 1979, 4, 6, 420. |
| 【4】 Bullock, M.W.; DE 1645975 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (rac)-(XII) | 39503 | 6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b][1,3]thiazole | C11H12N2S | 详情 | 详情 | |
| (VII) | 10315 | 2-Bromo-1-phenyl-ethanone; 2-Bromo-1-phenyl-1-ethanone | 70-11-1 | C8H7BrO | 详情 | 详情 |
| (VIII) | 39504 | 4,5-dihydro-1,3-thiazol-2-ylamine; 4,5-dihydro-1,3-thiazol-2-amine | 1779-81-3 | C3H6N2S | 详情 | 详情 |
| (IX) | 39505 | 2-(2-imino-1,3-thiazolidin-3-yl)-1-phenyl-1-ethanone | C11H12N2OS | 详情 | 详情 | |
| (X) | 39506 | 2-(2-imino-1,3-thiazolidin-3-yl)-1-phenyl-1-ethanol | C11H14N2OS | 详情 | 详情 | |
| (XI) | 39507 | N-[3-(2-hydroxy-2-phenylethyl)-1,3-thiazolidin-2-yl]acetamide | C13H18N2O2S | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(rac)-(XII)The inactive d-(+)-levamisole can be isomerized by reaction with a strong nonaqueous base such as potassium tert-butylate, sodium amide or sodium hydride with or without solvent (DMF, DMSO). The racemic mixture obtained is resolved in its optical isomers through the d-10-camphorsulfonate, N-benzene (or p-toluene)sulfonyl-L-(+)-glutamic salt.
| 【1】 US 3579530 . |
| 【2】 Bullock, M.W.; DE 1645975 . |
| 【3】 Castañer, J.; Hopkins, S.J.; Blancafort, P.; Serradell, M.N.; Levamisole hydrochloride. Drugs Fut 1979, 4, 6, 420. |
| 【4】 Bullock, M.W.; Hand, J.J.; US 3673206 . |