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【结 构 式】 
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【分子编号】56269 【品名】(2R,4S)-1-[(3aS,9bS)-2,2-dimethyl-3a,9b-dihydro-2H-chromeno[4,3-d][1,3]oxazol-1(4H)-yl]-2-benzyl-4-hydroxy-5-iodo-1-pentanone 【CA登记号】 |
【 分 子 式 】C24H28INO4 【 分 子 量 】521.39513 【元素组成】C 55.29% H 5.41% I 24.34% N 2.69% O 12.27% |
合成路线1
该中间体在本合成路线中的序号：(XXIV)Bromochromanone (XVI) was prepared by bromination of 4-chromanone (XV). Subsequent reduction of (XVI) with NaBH4 provided bromohydrin (XVII). Ritter reaction of (XVII) with acetonitrile and sulfuric acid, followed by acidic hydrolysis, led to racemic cis-3-bromo-4-chromanol, which was then resolved by means of (S)-(+)-mandelic acid. The desired (S,S)-isomer (XVIII) was coupled with hydrocinnamic acid (XIX) giving amide (XX). After protection of hydroxy amide (XX) as the acetonide (XXI), the lithium enolate of amide (XXI) was alkylated with allyl bromide (XXII) to furnish the (S)-2-benzyl-4-pentenamide (XXIII) as the main diastereoisomer. Halogenation of (XXIII) with N-iodosuccinimide in H2O-EtOAc afforded iodohydrin (XXIV), which was cyclized to epoxide (XXV) in the presence of NaOMe.
| 【1】 gamma-Hydroxy-2-(fluoroalkylaminocarbonyl)-1-piperazinepentanamides as HIV protease inhibitors. EP 1242426; WO 0138332 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XV) | 14461 | 2,3-Dihydro-4H-chromen-4-one; 4-Chromanone | 491-37-2 | C9H8O2 | 详情 | 详情 |
| (XVI) | 56263 | 3-bromo-2,3-dihydro-4H-chromen-4-one | C9H7BrO2 | 详情 | 详情 | |
| (XVII) | 56264 | 3-bromo-4-chromanol | C9H9BrO2 | 详情 | 详情 | |
| (XVIII) | 56265 | (3S,4S)-4-amino-3,4-dihydro-2H-chromen-3-ol | C9H11NO2 | 详情 | 详情 | |
| (XIX) | 49181 | Hydrocinnamic acid; 3-Phenylpropionic acid; Benzylacetic acid | 501-52-0 | C9H10O2 | 详情 | 详情 |
| (XX) | 56266 | N-[(3S,4S)-3-hydroxy-3,4-dihydro-2H-chromen-4-yl]-3-phenylpropanamide | C18H19NO3 | 详情 | 详情 | |
| (XXI) | 56267 | 1-[(3aS,9bS)-2,2-dimethyl-3a,9b-dihydro-2H-chromeno[4,3-d][1,3]oxazol-1(4H)-yl]-3-phenyl-1-propanone | C21H23NO3 | 详情 | 详情 | |
| (XXII) | 11463 | 3-Bromo-1-propene; 3-Bromopropene；allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
| (XXIII) | 56268 | (2S)-1-[(3aS,9bS)-2,2-dimethyl-3a,9b-dihydro-2H-chromeno[4,3-d][1,3]oxazol-1(4H)-yl]-2-benzyl-4-penten-1-one | C24H27NO3 | 详情 | 详情 | |
| (XXIV) | 56269 | (2R,4S)-1-[(3aS,9bS)-2,2-dimethyl-3a,9b-dihydro-2H-chromeno[4,3-d][1,3]oxazol-1(4H)-yl]-2-benzyl-4-hydroxy-5-iodo-1-pentanone | C24H28INO4 | 详情 | 详情 | |
| (XXV) | 56270 | (2R)-1-[(3aS,9bS)-2,2-dimethyl-3a,9b-dihydro-2H-chromeno[4,3-d][1,3]oxazol-1(4H)-yl]-2-benzyl-3-[(2S)oxiranyl]-1-propanone | C24H27NO4 | 详情 | 详情 |