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【结 构 式】 
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【分子编号】51152 【品名】2,5-Dibromotoluene 【CA登记号】615-59-8 |
【 分 子 式 】C7H6Br2 【 分 子 量 】249.93264 【元素组成】C 33.64% H 2.42% Br 63.94% |
合成路线1
该中间体在本合成路线中的序号：(I)Lithiation of 2,5-dibromotoluene (I) with n-butyllithium at -75 C produced a mixture of 5-lithio (II) and 2-lithio (III) toluenes. Addition of this mixture to N-Boc-4-piperidone (IV) at low temperature provided the desired carbinol (V) and the corresponding 2-tolyl regioisomer, which were separated by flash chromatography (1). Alternatively, carbinol (V) was obtained by regioselective metallation of 2-bromo-5-iodotoluene (VI) and then addition to N-Boc-4-piperidone (IV). Dehydration of carbinol (V) with concomitant N-Boc group cleavage under acidic conditions furnished the tetrahydropyridine (VII). This was sulfonylated with methyl chlorosulfonylacetate (VIII) in the presence of either N,O-bis(trimethylsilyl)acetamide or diazabicycloundecene, producing sulfonamide (IX). Suzuki coupling of aryl bromide (IX) with 3-ethoxyphenylboronic acid (X) gave biphenyl (XI). The methyl ester group of (XI) was then condensed with hydroxylamine to afford the title hydroxamic acid.
| 【1】 Dack, K.N.; et al.; Design and synthesis of a novel series of matrix metalloproteinase inhibitors with high selectivity for MMP-3. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 260. |
| 【2】 Whitlock, G.A.; Dack, K.N. (Pfizer Inc.); Hydroxamic acid derivs. as matrix metalloprotease (MMP) inhibitors. EP 1036062; JP 2001525396; WO 9929667 . |
| 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) | 51152 | 2,5-Dibromotoluene | 615-59-8 | C7H6Br2 | 详情 | 详情 |
| (II) | 51153 | (4-bromo-3-methylphenyl)lithium | C7H6BrLi | 详情 | 详情 | |
| (III) | 51154 | (4-bromo-2-methylphenyl)lithium | C7H6BrLi | 详情 | 详情 | |
| (IV) | 18620 | tert-butyl 4-oxo-1-piperidinecarboxylate;BOC-Piperidone;N-(tert-Butoxycarbonyl)-4-piperidone; N-Boc-4-piperidone | 79099-07-3 | C10H17NO3 | 详情 | 详情 |
| (V) | 51155 | tert-butyl 4-(4-bromo-3-methylphenyl)-4-hydroxy-1-piperidinecarboxylate | C17H24BrNO3 | 详情 | 详情 | |
| (VI) | 51156 | 2-Bromo-5-iodotoluene | C7H6BrI | 详情 | 详情 | |
| (VII) | 51157 | 4-(4-bromo-3-methylphenyl)-1,2,3,6-tetrahydropyridine | C12H14BrN | 详情 | 详情 | |
| (VIII) | 51158 | methyl 2-(chlorosulfonyl)acetate | C3H5ClO4S | 详情 | 详情 | |
| (IX) | 51159 | methyl 2-[[4-(4-bromo-3-methylphenyl)-3,6-dihydro-1(2H)-pyridinyl]sulfonyl]acetate | C15H18BrNO4S | 详情 | 详情 | |
| (X) | 51160 | 3-Ethoxyphenylboronic acid | C8H11BO3 | 详情 | 详情 | |
| (XI) | 51151 | 2-(5-[[(3R)-3-(dimethylamino)pyrrolidinyl]sulfonyl]-2-propoxyphenyl)-5-[(4-fluorobenzyl)amino]-8-(4-methoxybenzyl)-3,8-dihydro-4H-pyrazolo[4',3':5,6]pyrido[4,3-d]pyrimidin-4-one | C38H41FN8O5S | 详情 | 详情 |