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【结 构 式】 
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【分子编号】50584 【品名】(2R)-N-[(1S,2S)-2-hydroxy-1-methyl-2-phenylethyl]-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-N,3-dimethylbutanamide 【CA登记号】 |
【 分 子 式 】C27H39NO5 【 分 子 量 】457.6104 【元素组成】C 70.87% H 8.59% N 3.06% O 17.48% |
合成路线1
该中间体在本合成路线中的序号：(XLII)Alternatively, the chiral phenylpropyl chloride (XXX) can also be prepared as follows: Reduction of the cinnamic acid (XXXVI) with H2 over Pd/C in ethyl acetate gives the phenylpropionic acid (XXXVII), which is treated with oxalyl chloride to yield the acyl chloride (XXXVIII). Condensation of (XXXVIII) with (+)-pseudoephedrine (XXXIX) by means of NaOH in toluene/water affords the chiral amide (XL), which is enantioselectively alkylated with 2-iodopropane (XLI) by means of LDA in THF to provide the adduct (XLII). Reduction of the amide group of (XLII) with BH3/NH3 in THF gives the already reported primary alcohol (XXIX), which is finally treated with POCl3 in hot toluene to afford the phenylpropyl chloride intermediate (XXX).
| 【1】 Mealy, N.E.; Castañer, R.M.; Silvestre, J.S.; Castañer, J.; Aliskiren Fumarate. Drugs Fut 2001, 26, 12, 1139. |
| 【2】 Carey, J.S.; Sandham, D.A.; Taylor, R.J.; Fassler, A.; A convergent synthesis of the renin inhibitor CGP60536B. Tetrahedron Lett 2000, 41, 51, 10091. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXIX) | 50573 | (2R)-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methyl-1-butanol | C17H28O4 | 详情 | 详情 | |
| (XXX) | 50574 | 4-[(2R)-2-(chloromethyl)-3-methylbutyl]-1-methoxy-2-(3-methoxypropoxy)benzene; 3-[5-[(2R)-2-(chloromethyl)-3-methylbutyl]-2-methoxyphenoxy]propyl methyl ether | 324763-39-5 | C17H27ClO3 | 详情 | 详情 |
| (XXXVI) | 50580 | (E)-3-[4-methoxy-3-(3-methoxypropoxy)phenyl]-2-propenoic acid | C14H18O5 | 详情 | 详情 | |
| (XXXVII) | 50581 | 3-[4-methoxy-3-(3-methoxypropoxy)phenyl]propionic acid | C14H20O5 | 详情 | 详情 | |
| (XXXVIII) | 50582 | 3-[4-methoxy-3-(3-methoxypropoxy)phenyl]propanoyl chloride | C14H19ClO4 | 详情 | 详情 | |
| (XXXIX) | 34409 | (1S,2S)-2-(methylamino)-1-phenyl-1-propanol | 90-82-4 | C10H15NO | 详情 | 详情 |
| (XL) | 50583 | N-[(1S,2S)-2-hydroxy-1-methyl-2-phenylethyl]-3-[4-methoxy-3-(3-methoxypropoxy)phenyl]-N-methylpropanamide | C24H33NO5 | 详情 | 详情 | |
| (XLI) | 19369 | 2-iodopropane | 75-30-9 | C3H7I | 详情 | 详情 |
| (XLII) | 50584 | (2R)-N-[(1S,2S)-2-hydroxy-1-methyl-2-phenylethyl]-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-N,3-dimethylbutanamide | C27H39NO5 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)
| 【1】 Sandham DA, Taylor RJ, Carey JS, et al. 2000. A convergent synthesis of the renin inhibitory CGP60536B. Tetrahedron Lett, 41(51): 10091～10094 |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 50585 | N-[(1S,2S)-2-hydroxy-1-methyl-2-phenylethyl]-N,3-dimethylbutanamide | C15H23NO2 | 详情 | 详情 | |
| (I) | 50580 | (E)-3-[4-methoxy-3-(3-methoxypropoxy)phenyl]-2-propenoic acid | C14H18O5 | 详情 | 详情 | |
| (II) | 50583 | N-[(1S,2S)-2-hydroxy-1-methyl-2-phenylethyl]-3-[4-methoxy-3-(3-methoxypropoxy)phenyl]-N-methylpropanamide | C24H33NO5 | 详情 | 详情 | |
| (III) | 50584 | (2R)-N-[(1S,2S)-2-hydroxy-1-methyl-2-phenylethyl]-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-N,3-dimethylbutanamide | C27H39NO5 | 详情 | 详情 | |
| (IV) | 50573 | (2R)-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methyl-1-butanol | C17H28O4 | 详情 | 详情 | |
| (V) | 50574 | 4-[(2R)-2-(chloromethyl)-3-methylbutyl]-1-methoxy-2-(3-methoxypropoxy)benzene; 3-[5-[(2R)-2-(chloromethyl)-3-methylbutyl]-2-methoxyphenoxy]propyl methyl ether | 324763-39-5 | C17H27ClO3 | 详情 | 详情 |
| (VII) | 50586 | (2S)-N-[(1S,2S)-2-hydroxy-1-methyl-2-phenylethyl]-2-isopropyl-N-methyl-4-pentenamide | C18H27NO2 | 详情 | 详情 | |
| (VIII) | 50587 | (2S,3S,5R,7S,9S)-7-(bromomethyl)-9-isopropyl-3,4-dimethyl-2-phenyl-1,6-dioxa-4-azaspiro[4.4]nonane | C18H26BrNO2 | 详情 | 详情 | |
| (IX) | 50588 | [(2S,3S,5R,7S,9S)-9-isopropyl-3,4-dimethyl-2-phenyl-1,6-dioxa-4-azaspiro[4.4]non-7-yl]methanol | C18H27NO3 | 详情 | 详情 | |
| (X) | 50589 | (2S,3S,5R,7S,9S)-9-isopropyl-3,4-dimethyl-2-phenyl-1,6-dioxa-4-azaspiro[4.4]nonane-7-carbaldehyde | C18H25NO3 | 详情 | 详情 | |
| (XI) | 50576 | (3S,5S)-5-[(1R,3S)-1-hydroxy-3-[4-methoxy-3-(3-methoxypropoxy)benzyl]-4-methylpentyl]-3-isopropyldihydro-2(3H)-furanone | C25H40O6 | 详情 | 详情 | |
| (XII) | 50578 | (3S,5S)-5-[(1S,3S)-1-azido-3-[4-methoxy-3-(3-methoxypropoxy)benzyl]-4-methylpentyl]-3-isopropyldihydro-2(3H)-furanone | C25H39N3O5 | 详情 | 详情 | |
| (XIII) | 28129 | 3-amino-2,2-dimethylpropanamide | 324763-51-1 | C5H12N2O | 详情 | 详情 |
| (XIV) | 61613 | (2S,4S,5S,7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-5-azido-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxypropoxy)benzyl]-8-methylnonanamide | C30H51N5O6 | 详情 | 详情 |