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【结 构 式】 
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【分子编号】18091 【品名】(1S)-1-[(4R,5R)-5-[(1S)-1-amino-2-phenylethyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-2-phenylethylamine; (1S)-1-[(4R,5R)-5-[(1S)-1-amino-2-phenylethyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-2-phenyl-1-ethanamine 【CA登记号】 |
【 分 子 式 】C21H28N2O2 【 分 子 量 】340.4656 【元素组成】C 74.08% H 8.29% N 8.23% O 9.4% |
合成路线1
该中间体在本合成路线中的序号：(XI)In an alternative method, the diamino ketal (XI) was subjected to reductive alkylation with m-nitrobenzaldehyde (XII) using sodium cyanoborohydride, sodium triacetoxyborohydride, or pyridine-borane complex as the reducing reagents to produce the bis-benzylamine (XIII). Cyclization of diamine (XIII) to urea (XIV) was accomplished by means of either phosgene or triphosgene in the presence of diisopropyl ethylamine. Subsequent ketal hydrolysis in (XIV) with methanesulfonic acid in MeOH yielded the dinitro precursor (X), which was finally reduced to the title compound by the same method as above.
| 【1】 Confalone, P.N.; Smyser, T.E. (Bristol-Myers Squibb Co.); Method for preparing N,N'-disubstd. cyclic ureas. WO 9639393 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 59260 | (4R,5S,6S,7R)-4,7-dibenzyl-5,6-dihydroxy-1,3-bis(3-nitrobenzyl)-1,3-diazepan-2-one | C33H32N4O7 | 详情 | 详情 | |
| (XI) | 18091 | (1S)-1-[(4R,5R)-5-[(1S)-1-amino-2-phenylethyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-2-phenylethylamine; (1S)-1-[(4R,5R)-5-[(1S)-1-amino-2-phenylethyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-2-phenyl-1-ethanamine | C21H28N2O2 | 详情 | 详情 | |
| (XII) | 12646 | 3-Nitrobenzaldehyde | 99-61-6 | C7H5NO3 | 详情 | 详情 |
| (XIII) | 59261 | (1R)-1-((4S,5S)-2,2-dimethyl-5-{(1R)-1-[(3-nitrobenzyl)amino]-2-phenylethyl}-1,3-dioxolan-4-yl)-N-(3-nitrobenzyl)-2-phenyl-1-ethanamine; N-[(1R)-1-((4S,5S)-2,2-dimethyl-5-{(1R)-1-[(3-nitrobenzyl)amino]-2-phenylethyl}-1,3-dioxolan-4-yl)-2-phenylethyl]-N-(3-nitrobenzyl)amine | C35H38N4O6 | 详情 | 详情 | |
| (XIV) | 59262 | (3aS,4R,8R,8aS)-4,8-dibenzyl-2,2-dimethyl-5,7-bis(3-nitrobenzyl)hexahydro-6H-[1,3]dioxolo[4,5-e][1,3]diazepin-6-one | C36H36N4O7 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)Diol (I) was protected as the isopropylidene ketal (III) by reaction with 2,2-dimethoxypropane (II) and p-toluenesulfonic acid. Then, the N-carbobenzoxy groups of (III) were eliminated by hydrogenolysis on Pd/C to give the diamine (IV), and this was coupled with N-carbobenzoxy-valine (V) using O-benzotriazol-1-yl-tetramethyluronium hexafluorophosphate (HBTU) to afford (VI). A new sequence of hydrogenolytic Cbz deprotection to give diamine (VII) and coupling with N-carbobenzoxy-alanine (VIII) and HBTU provided (IX). Finally, the target compound was obtained by hydrolysis of the isopropylidene ketal in methanol containing p-toluenesulfonic acid.
| 【1】 Lee, T.; et al.; Analysis of the S3 and S3' subsite specificities of feline immunodeficiency virus (FIV) protease: Development of a broad-based protease inhibitor efficacious against FIV, SIV, and HIV in vitro and ex vivo. Proc Natl Acad Sci USA 1998, 95, 3, 939-944. |
| 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) | 16587 | benzyl (1S,2R,3R,4S)-1-benzyl-4-[[(benzyloxy)carbonyl]amino]-2,3-dihydroxy-5-phenylpentylcarbamate | C34H36N2O6 | 详情 | 详情 | |
| (II) | 10722 | 1-Methoxy-1-methylethyl methyl ether; 2,2-Dimethoxypropane | 77-76-9 | C5H12O2 | 详情 | 详情 |
| (III) | 18090 | benzyl (1S)-1-[(4R,5R)-5-((1S)-1-[[(benzyloxy)carbonyl]amino]-2-phenylethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-phenylethylcarbamate | C37H40N2O6 | 详情 | 详情 | |
| (IV) | 18091 | (1S)-1-[(4R,5R)-5-[(1S)-1-amino-2-phenylethyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-2-phenylethylamine; (1S)-1-[(4R,5R)-5-[(1S)-1-amino-2-phenylethyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-2-phenyl-1-ethanamine | C21H28N2O2 | 详情 | 详情 | |
| (V) | 18092 | (2S)-2-[[(benzyloxy)carbonyl]amino]-3-methylbutyric acid | C13H17NO4 | 详情 | 详情 | |
| (VI) | 18093 | benzyl (1S)-1-([[(1S)-1-((4R,5R)-5-[(1S)-1-[((2S)-2-[[(benzyloxy)carbonyl]amino]-3-methylbutanoyl)amino]-2-phenylethyl]-2,2-dimethyl-1,3-dioxolan-4-yl)-2-phenylethyl]amino]carbonyl)-2-methylpropylcarbamate | C47H58N4O8 | 详情 | 详情 | |
| (VII) | 18094 | (2S)-2-amino-N-[(1S)-1-[(4R,5R)-5-((1S)-1-[[(2S)-2-amino-3-methylbutanoyl]amino]-2-phenylethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-phenylethyl]-3-methylbutanamide | C31H46N4O4 | 详情 | 详情 | |
| (VIII) | 10445 | N-Carbobenzyloxy-L-alanine;N-Benzyloxycarbonyl-L-alanine;Carbobenzyloxy-L-alanine;Z-L-Alanine;Z-Ala-OH;BenzyloxycarbonylLalanine;N-Cbz-L-alanine | 1142-20-7 | C11H13NO4 | 详情 | 详情 |
| (IX) | 18095 | benzyl (1S)-2-[((1S)-1-[[((1S)-1-[(4R,5R)-5-[(1S,4S,7S)-1-benzyl-4-isopropyl-7-methyl-3,6,9-trioxo-11-phenyl-10-oxa-2,5,8-triazaundec-1-yl]-2,2-dimethyl-1,3-dioxolan-4-yl]-2-phenylethyl)amino]carbonyl]-2-methylpropyl)amino]-1-methyl-2-oxoethylcarbam | C53H68N6O10 | 详情 | 详情 |