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【结 构 式】 
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【分子编号】68550 【品名】(S)-3-methyl-1-((3aR,4R,6R,7aS)-3a,5,5-trimethylhexahydro-4,6-methanobenzo[d][1,3,2]dioxaborol-2-yl)butan-1-amine 2,2,2-trifluoroacetate 【CA登记号】 |
【 分 子 式 】C17H28BNO4.C2HF3O2 【 分 子 量 】371.251 【元素组成】C 61.47% H 7.87% B 2.91% F 15.35% N 3.77% O 8.62% |
合成路线1
该中间体在本合成路线中的序号：(IV)Condensation of 2,5-dichlorobenzoyl chloride (I) with glycine (II) in the presence of NaOH in H2O/THF gives 2-(2,5-dichlorobenzoylamino) acetic acid (III), which then couples with the 1,3,2-benzodioxaborolyl butanamine derivative (IV) by means of TBTU and DIEA in DMF to yield peptide (V). O-Deprotection of 1,3,2-benzodioxaborolane (V) by means of HCl and 2-methylisopropyl boronic acid in methanol/hexane affords boroxin derivative (VI), which is finally esterified with citric acid (VII) in THF or MIBK or acetonitrile or 2-Me-THF or acetone or EtOAc .
| 【1】 Elliott, E.L., Ferdous, A.J., Kaufman, M.J. et al. (Millennium Pharmaceuticals, Inc.). Boronate ester compounds and pharmaceutical compositions thereof. CN 102066386, EP 2318419, JP 2011524902, US 2009325903, WO 2009154737. |
| 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) | 68548 | 2,5-dichlorobenzoyl chloride;2,5-dichloro-benzoyl chlorid | 2905-61-5 | C7H3Cl3O | 详情 | 详情 |
| (II) | 20436 | glycine | 56-40-6 | C2H5NO2 | 详情 | 详情 |
| (III) | 68549 | 2-(2,5-dichlorobenzoylamino)acetic acid | C9H7Cl2NO3 | 详情 | 详情 | |
| (IV) | 68550 | (S)-3-methyl-1-((3aR,4R,6R,7aS)-3a,5,5-trimethylhexahydro-4,6-methanobenzo[d][1,3,2]dioxaborol-2-yl)butan-1-amine 2,2,2-trifluoroacetate | C17H28BNO4.C2HF3O2 | 详情 | 详情 | |
| (V) | 68551 | 2,5-dichloro-N-(2-(((S)-3-methyl-1-((3aR,4R,6R,7aS)-3a,5,5-trimethylhexahydro-4,6-methanobenzo[d][1,3,2]dioxaborol-2-yl)butyl)amino)-2-oxoethyl)benzamide | C24H33BCl2N2O4 | 详情 | 详情 | |
| (VII) | 13856 | 2-Hydroxy-1,2,3-propanetricarboxylic acid; Citric acid | 77-92-9 | C6H8O7 | 详情 | 详情 |