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【结 构 式】 
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【分子编号】23453 【品名】(1R,2S)-2-[(tert-butoxycarbonyl)amino]-1-cyano-3-phenylpropyl 4-(2-pyridinyl)benzoate 【CA登记号】 |
【 分 子 式 】C27H27N3O4 【 分 子 量 】457.5292 【元素组成】C 70.88% H 5.95% N 9.18% O 13.99% |
合成路线1
该中间体在本合成路线中的序号：(XVII)2) Intermediate (IX) can also be obtained as follows: The cyclization of 4-cyanobenzoic acid methyl ester (XII) with acetylene at 15 Atm by means of cobaltocene in toluene at 180 C gives 4-(2-pyridyl)benzoic acid methyl ester (XIII), which is saponified with NaOH in methanol to the corresponding acid (XIV). The activation of (XIV) with isobutyl chloroformate yields the mixed anhydride (XV), which is condensed with N-(tert-butoxycarbonyl)-L-phenylalaninal (XVI) and KCN in dichloromethane, affording (XVII). The reaction of (XVII) with tert-butyl carbazate (V) by means of acetic acid in methanol gives hydrazone (XVIII), which is reduced to hydrazine (XIX) by means of sodium cyanoborohydride in THF. The isomerization of (XIX) by means of 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTDE) in hot diglyme yields hydrazide (XX), which is finally reduced to intermediate (IX) with diisobutylaluminum hydride in dichloromethane/THF.
| 【1】 Fassler, A.; Steiner, H.; Bold, G.; Capraro, H.-G. (Novartis AG); Process for the preparation of hydrazine derivs. useful as intermediates for the preparation of peptide analogues. WO 9746514 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 23634 | acetylene | 74-86-2 | C2H2 | 详情 | 详情 |
| (V) | 10893 | tert-butyl 1-hydrazinecarboxylate; tert-butyl carbazate | 870-46-2 | C5H12N2O2 | 详情 | 详情 |
| (IX) | 23445 | tert-butyl 2-[(2S,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyl]-2-[4-(2-pyridinyl)benzyl]-1-hydrazinecarboxylate | C32H42N4O5 | 详情 | 详情 | |
| (XII) | 10169 | methyl 4-cyanobenzoate；4-Cyanobenzoic acid methyl ester | 1129-35-7 | C9H7NO2 | 详情 | 详情 |
| (XIII) | 23449 | methyl 4-(2-pyridinyl)benzoate | C13H11NO2 | 详情 | 详情 | |
| (XIV) | 23450 | 4-(2-pyridinyl)benzoic acid | C12H9NO2 | 详情 | 详情 | |
| (XV) | 23451 | 4-(2-Pyridyl)benzoic acid isobutoxycarbonyl anhydride | C17H17NO4 | 详情 | 详情 | |
| (XVI) | 14540 | tert-butyl N-[(1S)-1-benzyl-2-oxoethyl]carbamate | C14H19NO3 | 详情 | 详情 | |
| (XVII) | 23453 | (1R,2S)-2-[(tert-butoxycarbonyl)amino]-1-cyano-3-phenylpropyl 4-(2-pyridinyl)benzoate | C27H27N3O4 | 详情 | 详情 | |
| (XVIII) | 23454 | tert-butyl 2-((E,2R,3S)-3-[(tert-butoxycarbonyl)amino]-4-phenyl-2-[[4-(2-pyridinyl)benzoyl]oxy]butylidene)-1-hydrazinecarboxylate | C32H38N4O6 | 详情 | 详情 | |
| (XIX) | 23455 | tert-butyl 2-((2S,3S)-3-[(tert-butoxycarbonyl)amino]-4-phenyl-2-[[4-(2-pyridinyl)benzoyl]oxy]butyl)-1-hydrazinecarboxylate | C32H40N4O6 | 详情 | 详情 | |
| (XX) | 23457 | tert-butyl 2-[(2S,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyl]-2-[4-(2-pyridinyl)benzoyl]-1-hydrazinecarboxylate | C32H40N4O6 | 详情 | 详情 |