|
【结 构 式】 
|
【分子编号】36659 【品名】N-[(1R)-4-azido-1-[(1S,2R,6S,8S)-6,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]butyl](trimethyl)-N-(trimethylsilyl)silanamine; N-[(1R)-4-azido-1-[(1S,2R,6S,8S)-6,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]butyl]-N,N-bis(trimethylsilyl)amine 【CA登记号】 |
【 分 子 式 】C20H41BN4O2Si2 【 分 子 量 】436.5533 【元素组成】C 55.03% H 9.47% B 2.48% N 12.83% O 7.33% Si 12.87% |
合成路线1
该中间体在本合成路线中的序号：(VIII)The hydroboration of allyl bromide (I) with diisopinocampheylborane gives the 3-bromopropylboronic ester (II), which by treatment with acetaldehyde and water yields the boronic acid (III). The reaction of (III) with NaN3 and ethanol affords 3-azidoboronic acid ethyl ester (IV), which is transesterified with optically active pipanediol (V) giving the cyclic ester (VI). The homologation of (VI) with LDA, ZnCl2 and dichloromethane in THF yields the alpha-chlorobutylboronic ester (VII), which is aminated with hexamethyldisylazane (HMDS) and BuLi to provide the silylated alpha-aminoboronic ester (VIII). The desilylation of (VIII) with methanol, and its protection with benzyl chloroformate gives the protected alpha-aminoboronic ester (IX). The hydrogenation of the azido group of (IX) with H2 over PtO2 affords the 4-aminobutylboronic ester (X), which is treated with N,N'-bis(tert-butoxycarbonyl)thiourea (XI), HgCl2 and TEA in DMF to give the guanidine derivative (XII). Finally, this compound is hydrolyzed and deprotected with refluxing 6N HCl.
| 【1】 Lebarbier, C.; Carreaux, F.; Carboni, B.; Boucher, J.L.; Synthesis of boronic acid analogs of L-arginine as alternate substrates or inhibitors of nitric oxide synthase. Bioorg Med Chem Lett 1998, 8, 18, 2573. |
| 【2】 Lebarbier, C.; et al.; Synthesis of a boronic acid analogue of L-ornithine. Synthesis 1996, 1371. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 10101 | Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene | 501-53-1 | C8H7ClO2 | 详情 | 详情 | |
| (I) | 11463 | 3-Bromo-1-propene; 3-Bromopropene；allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
| (II) | 36654 | bis[[(1R,2S,3S,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]methyl] 3-bromopropylboronate | C25H44BBrO2 | 详情 | 详情 | |
| (III) | 36655 | 3-bromopropylboronic acid | C3H8BBrO2 | 详情 | 详情 | |
| (IV) | 36656 | diethyl 3-azidopropylboronate | C7H16BN3O2 | 详情 | 详情 | |
| (V) | 32535 | (1R,2S,3R,5R)-2,6,6-trimethylbicyclo[3.1.1]heptane-2,3-diol | C10H18O2 | 详情 | 详情 | |
| (VI) | 36657 | 3-[(1S,2R,6S,8S)-6,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]propyl azide; (1S,2R,6S,8S)-4-(3-azidopropyl)-6,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]decane | C13H22BN3O2 | 详情 | 详情 | |
| (VII) | 36658 | (4S)-4-chloro-4-[(1S,2R,6S,8S)-6,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]butyl azide; (1S,2R,6S,8S)-4-[(1S)-4-azido-1-chlorobutyl]-6,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]decane | C14H23BClN3O2 | 详情 | 详情 | |
| (VIII) | 36659 | N-[(1R)-4-azido-1-[(1S,2R,6S,8S)-6,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]butyl](trimethyl)-N-(trimethylsilyl)silanamine; N-[(1R)-4-azido-1-[(1S,2R,6S,8S)-6,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]butyl]-N,N-bis(trimethylsilyl)amine | C20H41BN4O2Si2 | 详情 | 详情 | |
| (IX) | 36660 | benzyl (1R)-4-azido-1-[(1S,2R,6S,8S)-6,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]butylcarbamate | C22H31BN4O4 | 详情 | 详情 | |
| (X) | 36661 | benzyl (1R)-4-amino-1-[(1S,2R,6S,8S)-6,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]butylcarbamate | C22H33BN2O4 | 详情 | 详情 | |
| (XI) | 21843 | tert-butyl [(tert-butoxycarbonyl)amino]carbothioylcarbamate | 145013-05-4 | C11H20N2O4S | 详情 | 详情 |
| (XII) | 36662 | benzyl (1R)-4-([[(tert-butoxycarbonyl)amino][(tert-butoxycarbonyl)imino]methyl]amino)-1-[(1S,2R,6S,8S)-6,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0(2,6)]dec-4-yl]butylcarbamate | C33H51BN4O8 | 详情 | 详情 |