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【结 构 式】 
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【分子编号】65046 【品名】4-allyl 3-(tert-butyl) (4R)-5,5-dimethyl-1,3-thiazolidine-3,4-dicarboxylate 【CA登记号】 |
【 分 子 式 】C14H23NO4S 【 分 子 量 】301.40696 【元素组成】C 55.79% H 7.69% N 4.65% O 21.23% S 10.64% |
合成路线1
该中间体在本合成路线中的序号：(IV)5,5-Dimethylthiazolidine-4-carboxylic acid (I) is protected as the N-Boc derivative (II), and subsequently treated with allyl bromide (III) and triethylamine to form the allyl ester (IV). Acidic Boc group cleavage in (IV) provides amino ester (V), which is further coupled to the lactone acid (VI) to furnish amide (VII). The allyl ester group of (VII) is then removed by treatment with morpholine and Pd(PPh3)4, yielding acid (VIII). This is then coupled to (3,5-dimethylisothiazol-4-yl)methyl amine (IX) employing EDC/HOAt to afford the corresponding amide (X). Lactone ring opening in (X) by hydrolysis with LiOH gives rise to the hydroxy acid (XI), which is further protected as the silyl ether (XII) employing t-butyldimethylsilyl triflate.
| 【1】 Bohn, J.; Lu, Z.; Raghavan, S.; Charest, M.; Stahlhut, M.; Rutkowski, C.A.; Himmelberger, A.L.; Olsen, D.B.; Scheleif, W.A.; Carella, A.; Gabryelski, L.; Jin, L.; Lin, J.H.; Tata, J.R.; Chapman, K.; Synthesis of highly potent HIV protease inhibitors with activity against protease resistant virus. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 205. |
| 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) | 34776 | (4R)-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid | 72778-00-8 | C6H11NO2S | 详情 | 详情 |
| (II) | 34777 | (4R)-3-(tert-butoxycarbonyl)-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid | C11H19NO4S | 详情 | 详情 | |
| (III) | 11463 | 3-Bromo-1-propene; 3-Bromopropene；allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
| (IV) | 65046 | 4-allyl 3-(tert-butyl) (4R)-5,5-dimethyl-1,3-thiazolidine-3,4-dicarboxylate | C14H23NO4S | 详情 | 详情 | |
| (V) | 65047 | allyl (4R)-5,5-dimethyl-1,3-thiazolidine-4-carboxylate | C9H15NO2S | 详情 | 详情 | |
| (VI) | 65048 | (2S,4R)-4-benzyl-5-oxotetrahydro-2-furancarboxylic acid | C12H12O4 | 详情 | 详情 | |
| (VII) | 65049 | allyl (4R)-3-{[(2S,4R)-4-benzyl-5-oxotetrahydro-2-furanyl]carbonyl}-5,5-dimethyl-1,3-thiazolidine-4-carboxylate | C21H25NO5S | 详情 | 详情 | |
| (VIII) | 65050 | (4R)-3-{[(2S,4R)-4-benzyl-5-oxotetrahydro-2-furanyl]carbonyl}-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid | C18H21NO5S | 详情 | 详情 | |
| (IX) | 65059 | (3,5-dimethyl-4-isothiazolyl)methanamine; (3,5-dimethyl-4-isothiazolyl)methylamine | C6H10N2S | 详情 | 详情 | |
| (X) | 65060 | (4R)-3-{[(2S,4R)-4-benzyl-5-oxotetrahydro-2-furanyl]carbonyl}-N-[(3,5-dimethyl-4-isothiazolyl)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide | C24H29N3O4S2 | 详情 | 详情 | |
| (XI) | 65061 | (2R,4S)-2-benzyl-5-[(4R)-4-({[(3,5-dimethyl-4-isothiazolyl)methyl]amino}carbonyl)-5,5-dimethyl-1,3-thiazolidin-3-yl]-4-hydroxy-5-oxopentanoic acid | C24H31N3O5S2 | 详情 | 详情 | |
| (XII) | 65062 | (2R,4S)-2-benzyl-4-{[tert-butyl(dimethyl)silyl]oxy}-5-[(4R)-4-({[(3,5-dimethyl-4-isothiazolyl)methyl]amino}carbonyl)-5,5-dimethyl-1,3-thiazolidin-3-yl]-5-oxopentanoic acid | C30H45N3O5S2Si | 详情 | 详情 |