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【结 构 式】 
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【分子编号】31327 【品名】(5-bromo-2-furyl)methanol 【CA登记号】 |
【 分 子 式 】C5H5BrO2 【 分 子 量 】176.9975 【元素组成】C 33.93% H 2.85% Br 45.14% O 18.08% |
合成路线1
该中间体在本合成路线中的序号：(II)5-Bromo-2-furoic acid (I) was converted to the mixed anhydride with isobutyl chloroformate and then reduced to alcohol (II) using NaBH4. After formation of the sodium alkoxide of (II) with NaH, condensation with chloride (III) in the presence of 15-crown-5 provided ether (IV). Hydrolysis of the methyl ester of (IV), followed by coupling of the resulting carboxylic acid (V) with L-methionine methyl ester (VI) gave amide (VII). Further Suzuki coupling of (VII) with 4-chlorophenyl boronic acid (VIII) produced the aryl-substituted furan (IX). Finally, hydrolysis of the methionine methyl ester of (IX) with LiOH, followed by lyophilization furnished the corresponding lithium carboxylate salt.
| 【1】 Augeri, D.J.; Kalvin, D.; Anowick, D.; et al.; Potent and orally bioavailable noncysteine-containing inhibitors of protein farnesyltransferase. Bioorg Med Chem Lett 1999, 9, 8, 1069. |
| 【2】 Donner, B.G.; Janowick, D.A.; Larsen, J.J.; Rosenberg, S.H.; Hamilton, A.D.; Barr, K.J.; Sorensen, B.K.; Augeri, D.J.; Kalvin, D.M.; O'Connor, S.J.; Fakhoury, S.A.; Swenson, R.E.; Liu, G.; Sebti, S.M.; Shen, W. (University of Pittsburgh); Inhibitors of protein isoprenyl transferases. EP 0986384; WO 9850029; WO 9850030; WO 9850031 . |
| 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) | 31326 | 5-bromo-2-furoic acid | 585-70-6 | C5H3BrO3 | 详情 | 详情 |
| (II) | 31327 | (5-bromo-2-furyl)methanol | C5H5BrO2 | 详情 | 详情 | |
| (III) | 31328 | methyl 5-(chloromethyl)-2'-methyl[1,1'-biphenyl]-2-carboxylate | C16H15ClO2 | 详情 | 详情 | |
| (IV) | 31329 | methyl 5-[[(5-bromo-2-furyl)methoxy]methyl]-2'-methyl[1,1'-biphenyl]-2-carboxylate | C21H19BrO4 | 详情 | 详情 | |
| (V) | 31330 | 5-[[(5-bromo-2-furyl)methoxy]methyl]-2'-methyl[1,1'-biphenyl]-2-carboxylic acid | C20H17BrO4 | 详情 | 详情 | |
| (VI) | 17950 | D-Methionine methyl ester; methyl (2S)-2-amino-4-(methylsulfanyl)butanoate hydrochloride | 21691-49-6 | C6H13NO2S | 详情 | 详情 |
| (VII) | 31331 | methyl (2S)-2-[[(5-[[(5-bromo-2-furyl)methoxy]methyl]-2'-methyl[1,1'-biphenyl]-2-yl)carbonyl]amino]-4-(methylsulfanyl)butanoate | C26H28BrNO5S | 详情 | 详情 | |
| (VIII) | 17575 | 4-chlorophenylboronic acid | 1679-18-1 | C6H6BClO2 | 详情 | 详情 |
| (IX) | 31332 | methyl (2S)-2-([[5-([[5-(4-chlorophenyl)-2-furyl]methoxy]methyl)-2'-methyl[1,1'-biphenyl]-2-yl]carbonyl]amino)-4-(methylsulfanyl)butanoate | C32H32ClNO5S | 详情 | 详情 |