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【结 构 式】 
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【分子编号】52470 【品名】4-({2-[{[(1,1-dimethylethyl)oxy]carbonyl}({[(1,1-dimethylethyl)oxy]carbonyl}oxy)amino]-3-[(phenylmethyl)oxy]propyl}oxy)-4'-[(trifluoromethyl)oxy]-1,1'-biphenyl 【CA登记号】 |
【 分 子 式 】C33H38F3NO8 【 分 子 量 】633.6618696 【元素组成】C 62.55% H 6.04% F 8.99% N 2.21% O 20.2% |
合成路线1
该中间体在本合成路线中的序号：(VIII)Suzuki coupling between 4-methoxyphenylboronic acid (I) and 1-bromo-4-(trifluoromethoxy)benzene (II) gave the biphenyl derivative (III). Methyl ether cleavage in (III) by means of BBr3 provided the biphenyl alcohol (IV), which was condensed with (S)-benzyl glycidyl ether (V) under basic conditions, yielding the chiral glycerol diether (VI). Mitsunobu coupling of alcohol (VI) with the di-Boc-protected hydroxylamine (VII) using DEAD/PPh3 afforded carbamate (VIII). Subsequent catalytic hydrogenolysis of the benzyl ether of (VIII) gave alcohol (IX). Condensation of this alcohol (IX) with 5,5-dimethylhydantoin (X) under Mitsunobu conditions, followed by acidic cleavage of the Boc protecting groups, furnished the hydroxylamine derivative (XI). This was finally N-formylated by treatment with formic acetic anhydride.
| 【1】 Curtin, M.L.; et al.; Discovery and characterization of the potent, selective and orally bioavailable MMP inhibitor ABT-770. Bioorg Med Chem Lett 2001, 11, 12, 1557. |
| 【2】 Dellaria, J.F. Jr.; Gong, J.; Steinman, D.H.; Michaelides, M.R.; Giesler, J.; Davidsen, S.K.; Curtin, M.L.; Florjancic, A.S.; Xu, L.; Guo, Y.; Holms, J.H.; Wada, C.K.; Heyman, H.R. (Abbott Laboratories Inc.); Reverse hydroxamate inhibitors of matrix metalloproteinases. JP 2001523272; WO 9906361 . |
| 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) | 39246 | 4-methoxyphenylboronic acid | 5720-07-0 | C7H9BO3 | 详情 | 详情 |
| (II) | 52466 | 4-Bromophenyl trifluoromethyl ether; 4-(Trifluoromethoxy)bromobenzene; 4-Bromo-(trifluoromethoxy)-benzene; 4-Bromo-alpha,alpha,alpha-trifluoroanisole; 4-Bromotrifluoromethoxybenzene; 1-Bromo-4-(trifluoromethoxy)benzene | 407-14-7 | C7H4BrF3O | 详情 | 详情 |
| (III) | 52467 | 4-(methyloxy)-4'-[(trifluoromethyl)oxy]-1,1'-biphenyl; methyl 4'-[(trifluoromethyl)oxy][1,1'-biphenyl]-4-yl ether | C14H11F3O2 | 详情 | 详情 | |
| (IV) | 52468 | 4'-[(trifluoromethyl)oxy][1,1'-biphenyl]-4-ol | C13H9F3O2 | 详情 | 详情 | |
| (V) | 12350 | Benzyl (2R)oxiranylmethyl ether; (2R)-2-[(Benzyloxy)methyl]oxirane | 14618-80-5 | C10H12O2 | 详情 | 详情 |
| (VI) | 52469 | 1-[(phenylmethyl)oxy]-3-({4'-[(trifluoromethyl)oxy][1,1'-biphenyl]-4-yl}oxy)-2-propanol | C23H21F3O4 | 详情 | 详情 | |
| (VII) | 34722 | 2-[([[(tert-butoxycarbonyl)amino]oxy]carbonyl)oxy]-2-methylpropane | C10H19NO5 | 详情 | 详情 | |
| (VIII) | 52470 | 4-({2-[{[(1,1-dimethylethyl)oxy]carbonyl}({[(1,1-dimethylethyl)oxy]carbonyl}oxy)amino]-3-[(phenylmethyl)oxy]propyl}oxy)-4'-[(trifluoromethyl)oxy]-1,1'-biphenyl | C33H38F3NO8 | 详情 | 详情 | |
| (IX) | 52471 | 4-({2-[{[(1,1-dimethylethyl)oxy]carbonyl}({[(1,1-dimethylethyl)oxy]carbonyl}oxy)amino]-3-hydroxypropyl}oxy)-4'-[(trifluoromethyl)oxy]-1,1'-biphenyl | C26H32F3NO8 | 详情 | 详情 | |
| (X) | 32473 | 5,5-dimethyl-2,4-imidazolidinedione | 77-71-4 | C5H8N2O2 | 详情 | 详情 |
| (XI) | 52472 | 3-[2-(hydroxyamino)-3-({4'-[(trifluoromethyl)oxy][1,1'-biphenyl]-4-yl}oxy)propyl]-5,5-dimethyl-2,4-imidazolidinedione | C21H22F3N3O5 | 详情 | 详情 |