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【结 构 式】 
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【分子编号】11901 【品名】2-(4-Hydroxycyclohexyl)-1H-isoindole-1,3(2H)-dione 【CA登记号】104618-31-7 |
【 分 子 式 】C14H15NO3 【 分 子 量 】245.27804 【元素组成】C 68.56% H 6.16% N 5.71% O 19.57% |
合成路线1
该中间体在本合成路线中的序号：(VII)This compound can be obtained in two related ways: 1) The cyclization of 4-acetamidocyclohexanone (I) with thiourea (II) by means of Br2 in hot acetic acid gives 6-acetamido-2-amino-4,5,6,7-tetrahydrobenzothiazole (III), which by hydrolysis with refluxing aqueous HBr yields racemic 2,6-diamino-4,5,6,7-tetrahydrobenzothiazole (racemic IV). Optical resolution with L-(+)-tartaric acid affords the (S)-(-)-isomer (IV), which is finally treated with propionaldehyde and LiBH4. 2) The reaction of 4-aminocyclohexanol (V) with phthalic anhydride (VI) in toluene gives the phthalimido derivative (VII), which is oxidized with potassium dichromate - H2SO4 to the corresponding cyclohexanone (VIII). The cyclization of (VIII) with thiourea (II) and Br2 as before affords 2-amino-6-phthalimido-4,5,6,7-tetrahydrobenzothiazole (IX), which is deprotected with hydrazine in refluxing ethanol yielding racemic (IV), already obtained.
| 【1】 Griss, G. et al. (Dr. Karl Thomae GmbH); Tetrahydrobenzothiazoles, their preparation and their use as intermediates or as medicines. AU 8551544; DE 3447075; DE 3508947; EP 0186087; ES 8707513; ES 8707514; ES 8707515; JP 1986155377; US 4731374 . |
| 【2】 Schneider, C.S.; Mierau, J.; J. Dopamine autoreceptor agonists: Resolution and pharmacological activity of 2,6-diaminotetrahydrobenzothiazole and an aminothiazole analogue of apomorphine. J Med Chem 1987, 30, 3, 494. |
| 【3】 De Angelis, L.; Pramipexole Hydrochloride. Drugs Fut 1992, 17, 4, 291. |
| 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) | 11895 | N-(4-Oxocyclohexyl)acetamide | 27514-08-5 | C8H13NO2 | 详情 | 详情 |
| (II) | 10180 | Thiourea | 62-56-6 | CH4N2S | 详情 | 详情 |
| (III) | 11897 | N-(2-Amino-4,5,6,7-tetrahydro-1,3-benzothiazol-6-yl)acetamide | 104617-51-8 | C9H13N3OS | 详情 | 详情 |
| (IV) | 11898 | (6S)-2-Amino-4,5,6,7-tetrahydro-1,3-benzothiazol-6-ylamine; (6S)-4,5,6,7-Tetrahydro-1,3-benzothiazole-2,6-diamine | C7H11N3S | 详情 | 详情 | |
| (V) | 11899 | 4-Aminocyclohexanol; trans-4-Aminocyclohexanol | 27489-62-9 | C6H13NO | 详情 | 详情 |
| (VI) | 11900 | 2-Benzofuran-1,3-dione;1,2-Benzenedicarboxylic Anhydride;1,2-BENZENE DICARBOXYLIC ACID ANHYDRIDE;1,2-BENZENEDICARBONIC ACID, ANHYDRIDE;1,3-DIOXOPHTHALAN;1,3-ISOBENZOFURANDIONE;o-phthalic anhydride; Phthalic anhydride | 85-44-9 | C8H4O3 | 详情 | 详情 |
| (VII) | 11901 | 2-(4-Hydroxycyclohexyl)-1H-isoindole-1,3(2H)-dione | 104618-31-7 | C14H15NO3 | 详情 | 详情 |
| (VIII) | 11902 | 2-(4-Hydroxycyclohexyl)-1H-isoindole-1,3(2H)-dione | C14H13NO3 | 详情 | 详情 | |
| (IX) | 11903 | 2-(2-Amino-4,5,6,7-tetrahydro-1,3-benzothiazol-6-yl)-1H-isoindole-1,3(2H)-dione | C15H13N3O2S | 详情 | 详情 |