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【结 构 式】 
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【分子编号】32879 【品名】4-hydroxy-6-phenethyl-6-propyl-5,6-dihydro-2H-pyran-2-one 【CA登记号】 |
【 分 子 式 】C16H20O3 【 分 子 量 】260.333 【元素组成】C 73.82% H 7.74% O 18.44% |
合成路线1
该中间体在本合成路线中的序号：(III)A new synthesis of PNU-140690 has been developed: The condensation of 1-phenyl-3-hexanone (I) with methyl acetoacetate (II) by means of NaH in THF, followed by cyclization gives the hydroxypyrone (III), which by condensation with 3-nitrobenzaldehyde (IV) by means of AlCl3 in THF yields the benzylidene-pyrone (V). The alkylation of (V) with Et3Al, CuBr-Me2S in THF affords intermediate (VI), which is reduced at the nitro group with H2 over Pd/C in methanol giving the racemic amine (VII). The optical resolution of the N-benzyloxycarbonyl derivative of (VII) with chiral HPLC yielded the desired (R,R)-enantiomer (VIII), which was finally sulfonated with 5-(trifluoromethyl)pyridine-2-sulfonyl chloride (IX) in pyridine/dichloromethane.
| 【1】 Turner, S.R.; Strohbach, J.W.; Tommasi, R.A.; Aristoff, P.A.; Johnson, P.D.; Skulnick, H.I.; Dolak, L.A.; Seest, E.P.; Tomich, P.K.; Bohanon, M.J.; Horng, M.M.; Lynn, J.C.; Chong, K.T.; Hinshaw, R.R.; Watenpaugh, K.D.; Janakiraman, M.N.; Thaisrivongs, S.; Tipranavir (PNU-140690): A potent, orally bioavailable nonpeptidic HIV protease inhibitor of the 5,6-dihydro-4-hydroxy-2-pyrone sulfonamide class. J Med Chem 1998, 41, 18, 3467. |
| 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) | 17233 | 1-phenyl-3-hexanone | C12H16O | 详情 | 详情 | |
| (II) | 11791 | methyl 3-oxobutanoate; Methyl acetoacetate | 105-45-3 | C5H8O3 | 详情 | 详情 |
| (III) | 32879 | 4-hydroxy-6-phenethyl-6-propyl-5,6-dihydro-2H-pyran-2-one | C16H20O3 | 详情 | 详情 | |
| (IV) | 12646 | 3-Nitrobenzaldehyde | 99-61-6 | C7H5NO3 | 详情 | 详情 |
| (V) | 32880 | 3-[(Z)-(3-nitrophenyl)methylidene]-6-phenethyl-6-propyldihydro-2H-pyran-2,4-dione | C23H23NO5 | 详情 | 详情 | |
| (VI) | 32881 | 4-hydroxy-3-[1-(3-nitrophenyl)propyl]-6-phenethyl-6-propyl-5,6-dihydro-2H-pyran-2-one | C25H29NO5 | 详情 | 详情 | |
| (VII) | 32882 | 3-[1-(3-aminophenyl)propyl]-4-hydroxy-6-phenethyl-6-propyl-5,6-dihydro-2H-pyran-2-one | C25H31NO3 | 详情 | 详情 | |
| (VIII) | 17236 | (6R)-3-[(1R)-1-(3-aminophenyl)propyl]-4-hydroxy-6-phenethyl-6-propyl-5,6-dihydro-2H-pyran-2-one | C25H31NO3 | 详情 | 详情 | |
| (IX) | 17237 | 5-(trifluoromethyl)-2-pyridinesulfonyl chloride | C6H3ClF3NO2S | 详情 | 详情 |