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【结 构 式】 
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【分子编号】18713 【品名】(7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)methanesulfonyl chloride 【CA登记号】 |
【 分 子 式 】C10H15ClO3S 【 分 子 量 】250.746 【元素组成】C 47.9% H 6.03% Cl 14.14% O 19.14% S 12.79% |
合成路线1
该中间体在本合成路线中的序号：(+)-(II)The condensation of (rac?-18-methoxycoronaridine with (S)-(+)-camphorsulfonyl chloride (II) by means of KHMDS in THF gives the corresponding mixture of the diastereomeric sulfonamides (-)-(+)-(III) and (+)-(+)-(III), which are separated by normal phase silica gel chromatography. Both diastereomers are treated with KOH in methanol, yielding the target (-)- and (+)-enantiomers.
| 【1】 Herr, R.J.; Maisonneuve, I.M.; King, C.-H.R.; Meckler, H.; Glick, S.D.; Trova, M.P.; Synthesis of enantiomerically pure (+)- and (-)-18-methoxycoronaridine hydrochloride and their preliminary assessment as anti-addictive agents. Bioorg Med Chem Lett 2000, 10, 5, 473. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (+)-(II) | 18713 | (7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)methanesulfonyl chloride | C10H15ClO3S | 详情 | 详情 | |
| (-)(+)-(II) | 51471 | methyl (1S,17R)-3-[[(7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)methyl]sulfonyl]-17-(2-methoxyethyl)-3,13-diazapentacyclo[13.3.1.0(2,10).0(4,9).0(13,18)]nonadeca-2(10),4,6,8-tetraene-1-carboxylate | C32H42N2O6S | 详情 | 详情 | |
| (+)(+)-(II) | 51472 | methyl (1R,17S)-3-[[(7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)methyl]sulfonyl]-17-(2-methoxyethyl)-3,13-diazapentacyclo[13.3.1.0(2,10).0(4,9).0(13,18)]nonadeca-2(10),4,6,8-tetraene-1-carboxylate | C32H42N2O6S | 详情 | 详情 | |
| (I) | 51470 | methyl (1S,17R)-17-(2-methoxyethyl)-3,13-diazapentacyclo[13.3.1.0(2,10).0(4,9).0(13,18)]nonadeca-2(10),4,6,8-tetraene-1-carboxylate | C22H28N2O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)The reaction of 3-tetrahydrofuroic acid (I) with diphenyl phosphoryl azide (DPPA) in refluxing dioxane gave the intermediate isocyanate (II), which was treated with benzyl alcohol (III) to yield carbamate (IV). Subsequent hydrogenolysis in the presence of Pd/C afforded racemic amine (V), which was resolved by treatment with S-(+)-10-camphorsulfonyl chloride (VI) in pyridine, followed by column chromatography and recrystallization from acetone of the resulting sulfonamide (VII). Then, hydrolysis in HCl-AcOH provided the S-amine (VIII). Condensation of amine (VIII) with 6-chloropurine riboside (IX) in the presence of triethylamine in refluxing MeOH furnished the title compound.
| 【1】 Sorbera, L.A.; Bayes, M.; Castañer, J.; Martín, L.; Tecadenoson. Drugs Fut 2002, 27, 9, 846. |
| 【2】 Lum, R.T.; Pfister, J.R.; Schow, S.R.; Wick, M.M.; Nelson, M.G.; Schreiner, G.F. (CV Therapeutics, Inc.); N6 Heterocyclic substd. adenosine derivs.. EP 0920438; EP 0992510; JP 2000501426; US 5789416; WO 9808855 . |
| 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) | 18708 | tetrahydro-3-furancarboxylic acid | 89364-31-8 | C5H8O3 | 详情 | 详情 |
| (II) | 18709 | tetrahydro-3-furanyl isocyanate; 3-isocyanatotetrahydrofuran | C5H7NO2 | 详情 | 详情 | |
| (III) | 18710 | Benzyl alcohol; Phenylmethanol | 100-51-6 | C7H8O | 详情 | 详情 |
| (IV) | 18711 | benzyl tetrahydro-3-furanylcarbamate | C12H15NO3 | 详情 | 详情 | |
| (V) | 18712 | tetrahydro-3-furanylamine; tetrahydro-3-furanamine | C4H9NO | 详情 | 详情 | |
| (VI) | 18713 | (7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)methanesulfonyl chloride | C10H15ClO3S | 详情 | 详情 | |
| (VII) | 18714 | (7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)-N-[(3S)tetrahydro-3-furanyl]methanesulfonamide | C14H23NO4S | 详情 | 详情 | |
| (VIII) | 18715 | (3S)tetrahydro-3-furanamine; (3S)tetrahydro-3-furanylamine | C4H9NO | 详情 | 详情 | |
| (IX) | 18716 | 6-chloropurine riboside; (2R,3R,4S,5R)-2-(6-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol | 2004-06-0 | C10H11ClN4O4 | 详情 | 详情 |