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【结 构 式】 
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【分子编号】18477 【品名】2-propanesulfonyl chloride 【CA登记号】10147-37-2 |
【 分 子 式 】C3H7ClO2S 【 分 子 量 】142.60608 【元素组成】C 25.27% H 4.95% Cl 24.86% O 22.44% S 22.49% |
合成路线1
该中间体在本合成路线中的序号：(A)The acetylation of 4-aminobenzophenone (I) with acetic anhydride in hot benzene gives 4-acetamidobenzophenone (II), which is nitrated with 90% HNO3 in acetic acid-acetic anhydride yielding 4-acetamido-3-nitrobenzophenone (III). The hydrolysis of (III) with H2SO4 affords 4-amino-3-nitrobenzophenone (IV), which is reduced with H2 over Raney-Ni in THF to give 3,4-diaminobenzophenone (V). The cyclization of (V) with cyanogen bromide in methanol-water gives rise to 2-amino-5-benzoylbenzimidazol (VI), which is treated with isopropylsulfonyl chloride (A) and NaH in dimethoxyethane affording 2-amino-1-isopropylsulfonyl-6-benzoylbenzimidazol (VII). Finally, this compound is treated with hydroxylamine hydrochloride in refluxing methanol.
| 【1】 Paget, C.J.; et al.; DE 2638551 . |
| 【2】 Castaner, J.; Hopkins, S.J.; AR-336. Drugs Fut 1980, 5, 3, 120. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 18477 | 2-propanesulfonyl chloride | 10147-37-2 | C3H7ClO2S | 详情 | 详情 |
| (I) | 39112 | 3-Aminobenzophenone; (3-aminophenyl)(phenyl)methanone | 2835-78-1 | C13H11NO | 详情 | 详情 |
| (II) | 39113 | N-(3-benzoylphenyl)acetamide | 58202-86-1 | C15H13NO2 | 详情 | 详情 |
| (III) | 39114 | N-(5-benzoyl-2-nitrophenyl)acetamide | C15H12N2O4 | 详情 | 详情 | |
| (IV) | 39115 | (3-amino-4-nitrophenyl)(phenyl)methanone | C13H10N2O3 | 详情 | 详情 | |
| (V) | 12830 | (3,4-Diaminophenyl)phenylmethanone; 3,4-Diaminobenzophenone | 39070-63-8 | C13H12N2O | 详情 | 详情 |
| (VI) | 39116 | (2-amino-1H-benzimidazol-6-yl)(phenyl)methanone | C14H11N3O | 详情 | 详情 | |
| (VII) | 39117 | [2-amino-1-(isopropylsulfonyl)-1H-benzimidazol-6-yl](phenyl)methanone | C17H17N3O3S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(X)N-Boc-D-(3-phenylpropyl)glycine (I) was esterified to benzyl ester (II), and then, tert-butoxycarbonyl group was cleaved by acidic treatment to give amine (III). This was coupled with N-Boc-2-aminoisobutyric acid (IV) in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide.HCl (EDC) and 1-hydroxybenzotriazole (HOBt) to afford dipeptide ester (V), from which the benzyl ester group was removed by hydrogenolysis in the presence of Pd/C. The resulting acid (VI) was condensed with 1-(2-nitrophenyl)piperazine (VII) in the presence of EDC and HOBt to produce piperazide (VIII). Subsequent reduction of the nitro group by hydrogenation in the presence of Raney-Ni gave aniline (IX), which was treated with 2-propanesulfonyl chloride (X) to yield sulfonamide (XI). Finally, the tert-butoxycarbonyl protecting group was removed by treatment either with HCl in EtOAc or with trifluoroacetic acid to afford the target compound as the hydrochloride or the trifluoroacetate salt, respectively.
| 【1】 Barakat, K.J.; Cheng, K.; Chan, W.W.; Butler, B.S.; Jacks, T.M.; Schleim, K.D.; Hora, D.F. Jr.; Hickey, G.J.; Smith, R.G.; Patchett, A.A.; Nargund, R.P.; Synthesis and biological activities of phenyl piperazine-based peptidomimetic growth hormone secretagogues. Bioorg Med Chem Lett 1998, 8, 11, 1431. |
| 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) | 18468 | (2R)-2-[(tert-butoxycarbonyl)amino]-5-phenylpentanoic acid | C16H23NO4 | 详情 | 详情 | |
| (II) | 18469 | benzyl (2R)-2-[(tert-butoxycarbonyl)amino]-5-phenylpentanoate | C23H29NO4 | 详情 | 详情 | |
| (III) | 18470 | benzyl (2R)-2-amino-5-phenylpentanoate | C18H21NO2 | 详情 | 详情 | |
| (IV) | 18471 | N-(tert-butoxycarbonyl)-2-methylalanine | 30992-29-1 | C9H17NO4 | 详情 | 详情 |
| (V) | 18472 | benzyl (2R)-2-([2-[(tert-butoxycarbonyl)amino]-2-methylpropanoyl]amino)-5-phenylpentanoate | C27H36N2O5 | 详情 | 详情 | |
| (VI) | 18473 | (2R)-2-([2-[(tert-butoxycarbonyl)amino]-2-methylpropanoyl]amino)-5-phenylpentanoic acid | C20H30N2O5 | 详情 | 详情 | |
| (VII) | 18474 | 1-(2-nitrophenyl)piperazine | C10H13N3O2 | 详情 | 详情 | |
| (VIII) | 18475 | tert-butyl 1,1-dimethyl-2-[((1R)-1-[[4-(2-nitrophenyl)-1-piperazinyl]carbonyl]-4-phenylbutyl)amino]-2-oxoethylcarbamate | C30H41N5O6 | 详情 | 详情 | |
| (IX) | 18476 | tert-butyl 2-[((1R)-1-[[4-(2-aminophenyl)-1-piperazinyl]carbonyl]-4-phenylbutyl)amino]-1,1-dimethyl-2-oxoethylcarbamate | C30H43N5O4 | 详情 | 详情 | |
| (X) | 18477 | 2-propanesulfonyl chloride | 10147-37-2 | C3H7ClO2S | 详情 | 详情 |
| (XI) | 18478 | tert-butyl 2-([(1R)-1-[(4-[2-[(isopropylsulfonyl)amino]phenyl]-1-piperazinyl)carbonyl]-4-phenylbutyl]amino)-1,1-dimethyl-2-oxoethylcarbamate | C33H49N5O6S | 详情 | 详情 |