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【结 构 式】 
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【分子编号】17226 【品名】(E)-2-pentenoyl chloride 【CA登记号】 |
【 分 子 式 】C5H7ClO 【 分 子 量 】118.56268 【元素组成】C 50.65% H 5.95% Cl 29.9% O 13.49% |
合成路线1
该中间体在本合成路线中的序号：(II)The condensation of 4(R)-phenyloxazolidin-2-one (I) with 2(E)-pentenoyl chloride (II) by means of BuLi in THF gives 3-[2(E)-pentenoyl]-3(R)-phenyloxazolidin-2-one (III), which is treated with 3-[bis(trimethylsilyl)amino]phenylmagnesium bromide (IV) and CuBr in DMSO/THF regioselectively yielding the addition product (V). Elimination of the silyl groups of (VII) in mild acidic conditions and treatment of the resulting amine with benzyl bromide affords the dibenzylated amine derivative (VI), which is regioselectively acylated with 2-methoxy-2-methyl-1,3-dioxolane (V) and TiCl4 in dichloromethane under basic conditions giving the dione (VIII). The condensation of (VIII) with 1-phenyl-3-hexanone (IX) by means of Ti(OBu)Cl3 in dichloromethane as before yields the hydroxy-dione (X), which is cyclized by means of potassium tert-butoxide in THF to afford the dihydropyrone (XI). The debenzylation of (XI) by hydrogenation with H2 over Pd/C in methanol/ethyl acetate gives the free amine (XII), which is finally sulfonated with 5-(trifluoromethyl)pyridine-2-sulfonyl chloride (XIII) in pyridine/dichloromethane
| 【1】 Graul, J.; Wroblewski, T.; Castañer, J.; PNU-140690. Drugs Fut 1998, 23, 2, 146. |
| 【2】 Romines, K.R.; Bundy, G.L.; Schwartz, T.M.; Tommasi, R.A.; Strohbach, J.W.; Turner, S.R.; Thaisrivongs, S.; Aristoff, P.A.; Johnson, P.D.; Skulnick, H.I.; Skaletzki, L.L.; Anderson, D.J.; Morris, J.; Gammill, R.B.; Luke, G.P. (Pharmacia Corp.); Pyranone cpds. useful to treat retroviral infections. EP 0758327; JP 1997512821; US 5852195; WO 9530670 . |
| 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) | 12173 | (4S)-4-Phenyl-1,3-oxazolan-2-one; (4S)-4-Phenyl-2-oxazolidinone; (S)-(+)-4-Phenyl-2-oxazolidinone | 99395-88-7 | C9H9NO2 | 详情 | 详情 |
| (II) | 17226 | (E)-2-pentenoyl chloride | C5H7ClO | 详情 | 详情 | |
| (III) | 17227 | (4R)-3-[(E)-2-pentenoyl]-4-phenyl-1,3-oxazolan-2-one | C14H15NO3 | 详情 | 详情 | |
| (IV) | 17228 | N-(3-methylphenyl)-N,N-bis(trimethylsilyl)amine; trimethyl-N-(3-methylphenyl)-N-(trimethylsilyl)silanamine | C13H25NSi2 | 详情 | 详情 | |
| (V) | 17229 | (4R)-3-((3S)-3-[3-[bis(trimethylsilyl)amino]phenyl]pentanoyl)-4-phenyl-1,3-oxazolan-2-one | C26H38N2O3Si2 | 详情 | 详情 | |
| (VI) | 17230 | (4R)-3-[(3S)-3-[3-(dibenzylamino)phenyl]pentanoyl]-4-phenyl-1,3-oxazolidin-2-one | C34H34N2O3 | 详情 | 详情 | |
| (VII) | 17231 | 2-methoxy-2-methyl-1,3-dioxolane; methyl 2-methyl-1,3-dioxolan-2-yl ether | C5H10O3 | 详情 | 详情 | |
| (VIII) | 17232 | (2S)-2-[(1S)-1-[3-(dibenzylamino)phenyl]propyl]-1-[(4R)-2-oxo-4-phenyl-1,3-oxazolidin-3-yl]-1,3-butanedione | C36H36N2O4 | 详情 | 详情 | |
| (IX) | 17233 | 1-phenyl-3-hexanone | C12H16O | 详情 | 详情 | |
| (X) | 17234 | (2S,5R)-2-[(1S)-1-[3-(dibenzylamino)phenyl]propyl]-5-hydroxy-1-[(4R)-2-oxo-4-phenyl-1,3-oxazolidin-3-yl]-5-phenethyl-1,3-octanedione | C48H52N2O5 | 详情 | 详情 | |
| (XI) | 17235 | (6R)-3-[(1R)-1-[3-(dibenzylamino)phenyl]propyl]-4-hydroxy-6-phenethyl-6-propyl-5,6-dihydro-2H-pyran-2-one | C39H43NO3 | 详情 | 详情 | |
| (XII) | 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 | |
| (XIII) | 17237 | 5-(trifluoromethyl)-2-pyridinesulfonyl chloride | C6H3ClF3NO2S | 详情 | 详情 |