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【结 构 式】 
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【分子编号】36228 【品名】2-imidazolidinone 【CA登记号】120-93-4 |
【 分 子 式 】C3H6N2O 【 分 子 量 】86.09352 【元素组成】C 41.85% H 7.02% N 32.54% O 18.58% |
合成路线1
该中间体在本合成路线中的序号：(V)C-10213-Go has been synthesized from 1-methyl-2-mercaptoimidazole (I). When (I) is methylated with methyl iodide it gives the corresponding thiomethyl derivative (II). Nitration of (II) yields the nitro derivative (III). Oxidation of (III) with monoperphthalic acid gives the sulfone (IV). Condensation of (IV) with 1-methanesulfonyl-2-imidazolidinone (VI) in the presence of sodium hydride affords C-10213-Go.
| 【1】 Arya, V.P.; Satranidazole. Drugs Fut 1983, 8, 9, 797. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (B) | 13467 | Methanesulfonyl chloride;Mesyl chloride;Methylsulfonyl chloride;Methanesulfonic acid chloride;Methanesulfonyl chloride;Methanesulphonyl chloride | 124-63-0 | CH3ClO2S | 详情 | 详情 |
| (A) | 34077 | 2-carboperoxybenzoic acid | C8H6O5 | 详情 | 详情 | |
| (I) | 18783 | 1-methyl-1H-imidazol-2-ylhydrosulfide; 1-methyl-1H-imidazole-2-thiol | 60-56-0 | C4H6N2S | 详情 | 详情 |
| (II) | 36225 | 1-methyl-2-(methylsulfanyl)-1H-imidazole; methyl 1-methyl-1H-imidazol-2-yl sulfide | C5H8N2S | 详情 | 详情 | |
| (III) | 36226 | methyl 1-methyl-5-nitro-1H-imidazol-2-yl sulfide; 1-methyl-2-(methylsulfanyl)-5-nitro-1H-imidazole | C5H7N3O2S | 详情 | 详情 | |
| (IV) | 36227 | 1-methyl-2-(methylsulfonyl)-5-nitro-1H-imidazole; methyl 1-methyl-5-nitro-1H-imidazol-2-yl sulfone | C5H7N3O4S | 详情 | 详情 | |
| (V) | 36228 | 2-imidazolidinone | 120-93-4 | C3H6N2O | 详情 | 详情 |
| (VI) | 36229 | 1-(methylsulfonyl)-2-imidazolidinone | 41730-79-4 | C4H8N2O3S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)Compound can be prepared in two different ways: 1) By condensation of ampicilline (aminobenzylpenicilline) (I) with 1-chlorocarbonyl-2-oxo-3-mehylsulfonylimidazolidine (II) by means of NaOH in cool water or triethylamine in THF-water. 2) By condensation of 6-aminopenicillanic acid (III) with D-[(3-methylsulfonyl-2-oxoimidazolidin-1-yl)carbonylamino]phenylacetic acid (IV) by means of tetramethylchloroformamidinium chloride (A) and N-methylmorpholine (B) in methylene chloride - THF. The phenylacetic acid (IV) is obtained by condensation of D-phenylglycine (V) with 1-chlorocarbonyl-2-oxo-3-mehylsulfonylimidazolidine (II) by means of NaOH in dioxane - water. The acid chloride (II) is prepared by reaction of 2-imidazolidone (VI) with methanesulfonyl chloride (VII) in refluxing THF to give N-methylsulfonyl-2-imidazolidone (VIII), which is then condensed with phosgene by means of trimethylchlorosilane and triethylamine in dioxane.
| 【1】 Koenig, H.B.; et al.; Penicillin compounds their production and their medicinal use. DE 2152968; FR 2157909; GB 1392850; JP 48049788; JP 48049911 . |
| 【2】 Koenig, H.B.; et al.; Penicillins their production and their medicinal use. DE 2152967; FR 2157908; GB 1392849; JP 48049787; JP 48049910 . |
| 【3】 Schroeck, W.; et al.; Penicillanic acids their production and their medicinal use. DE 2318955; ES 425197; FR 2225151; GB 1465355; JP 49135990 . |
| 【4】 Playle, A.C.; Castañer, J.; Mezlocillin. Drugs Fut 1977, 2, 9, 600. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (B) | 28928 | 4-methylmorpholine | 109-02-4 | C5H11NO | 详情 | 详情 |
| (A) | 40169 | N-[chloro(dimethylamino)methylene]-N-methylmethanaminium chloride | C5H12Cl2N2 | 详情 | 详情 | |
| (I) | 31107 | (2S,5R,6R)-6-[[(2R)-2-amino-2-phenylethanoyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid | 69-53-4 | C16H19N3O4S | 详情 | 详情 |
| (II) | 40167 | 3-(methylsulfonyl)-2-oxo-1-imidazolidinecarbonyl chloride | 41762-76-9 | C5H7ClN2O4S | 详情 | 详情 |
| (III) | 32631 | (2S,5R,6R)-6-amino-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; (+)-6-Aminopenicillanic acid; 6-APA | 551-16-6 | C8H12N2O3S | 详情 | 详情 |
| (IV) | 40168 | (2R)-2-([[3-(methylsulfonyl)-2-oxo-1-imidazolidinyl]carbonyl]amino)-2-phenylethanoic acid | C13H15N3O6S | 详情 | 详情 | |
| (V) | 40170 | (2R)-2-amino-2-phenylethanoic acid | C8H9NO2 | 详情 | 详情 | |
| (VI) | 36228 | 2-imidazolidinone | 120-93-4 | C3H6N2O | 详情 | 详情 |
| (VII) | 13467 | Methanesulfonyl chloride;Mesyl chloride;Methylsulfonyl chloride;Methanesulfonic acid chloride;Methanesulfonyl chloride;Methanesulphonyl chloride | 124-63-0 | CH3ClO2S | 详情 | 详情 |
| (VIII) | 36229 | 1-(methylsulfonyl)-2-imidazolidinone | 41730-79-4 | C4H8N2O3S | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XII)The reaction of N-(benzyloxycarbonyl)-L-valine (I) with paraformaldehyde and Ts-OH gives the oxazolidinone (II), which is treated with trimethyl trifluoromethylsilane and CsF in THF to yield the trifluoromethyloxazolidine (III). The cleavage of the oxazolidine ring of (III) by means of ZnCl2 and NaBH4 in t-butyl methyl ether affords the protected aminoalcohol (IV), which is deprotected by means of H2 over Pd(OH)2 in ethyl acetate to provide the free aminoalcohol (V). The condensation of (V) with N-(benzyloxycarbonyl)-L-valyl-L-proline (VI) by means of EDC in dichloromethane gives the protected tripeptide analogue (VII), which is deprotected with H2 over Pd(OH)2 in ethanol to yield the tripeptide analogue (VIII). The condensation of (VIII) with the imidazolidinoneacetic acid derivative (IX) by means of EDC, as before, affords the acylated tripeptide (X), which is oxidized with DMP in dichloromethane to provide the acylated-L-valyl-L-prolyl-L-valyl-trifluoromethane (XI). Finally, this compound is deprotected with TFA in dichloromethane to give the target peptide analogue. The imidazolidinoneacetic acid derivative (IX) intermediate is obtained as follows: the reaction of 2-imidazolidinone (XII) with tert-butyl 2-bromoacetate (XIII) by means of lithium tert-butoxide in DMF gives the bis tert-butyl acetate (XIV), which is selectively monohydrolyzed by means of KOH in hot ethanol/water to afford the target imidazolidinoneacetic acid derivative (IX).
| 【1】 Sato, F.; Inoue, Y.; Honda, S.; Komiya, M.; Takemura, T.; Omodani, T.; Shiratake, R. (Dainippon Pharmaceutical Co., Ltd.); Heterocyclic cpds., intermediates thereof and elastase inhibitors. EP 1157998; JP 2000256396; WO 0052032 . |
| 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) | 18092 | (2S)-2-[[(benzyloxy)carbonyl]amino]-3-methylbutyric acid | C13H17NO4 | 详情 | 详情 | |
| (II) | 55779 | benzyl (4S)-4-isopropyl-5-oxo-1,3-oxazolidine-3-carboxylate | C14H17NO4 | 详情 | 详情 | |
| (III) | 55780 | benzyl (4S,5R)-5-hydroxy-4-isopropyl-5-(trifluoromethyl)-1,3-oxazolidine-3-carboxylate | C15H18F3NO4 | 详情 | 详情 | |
| (IV) | 55781 | benzyl (1S,2S)-3,3,3-trifluoro-2-hydroxy-1-isopropylpropylcarbamate | C14H18F3NO3 | 详情 | 详情 | |
| (V) | 55782 | (2S,3S)-3-amino-1,1,1-trifluoro-4-methyl-2-pentanol | C6H12F3NO | 详情 | 详情 | |
| (VI) | 22787 | (2S)-1-((2S)-2-[[(benzyloxy)carbonyl]amino]-3-methylbutanoyl)-2-pyrrolidinecarboxylic acid | C18H24N2O5 | 详情 | 详情 | |
| (VII) | 55783 | benzyl (1S)-2-methyl-1-{[(2S)-2-({[(1S,2S)-3,3,3-trifluoro-2-hydroxy-1-isopropylpropyl]amino}carbonyl)pyrrolidinyl]carbonyl}propylcarbamate | C24H34F3N3O5 | 详情 | 详情 | |
| (VIII) | 55784 | (2S)-1-[(2S)-2-amino-3-methylbutanoyl]-N-[(1S,2S)-3,3,3-trifluoro-2-hydroxy-1-isopropylpropyl]-2-pyrrolidinecarboxamide | C16H28F3N3O3 | 详情 | 详情 | |
| (IX) | 55785 | 2-{3-[2-(tert-butoxy)-2-oxoethyl]-2-oxo-1-imidazolidinyl}acetic acid | C11H18N2O5 | 详情 | 详情 | |
| (X) | 55786 | tert-butyl 2-(3-{2-[((1S)-2-methyl-1-{[(2S)-2-({[(1S,2S)-3,3,3-trifluoro-2-hydroxy-1-isopropylpropyl]amino}carbonyl)pyrrolidinyl]carbonyl}propyl)amino]-2-oxoethyl}-2-oxo-1-imidazolidinyl)acetate | C27H44F3N5O7 | 详情 | 详情 | |
| (XI) | 55787 | tert-butyl 2-(3-{2-[((1S)-2-methyl-1-{[(2S)-2-({[(1S)-3,3,3-trifluoro-1-isopropyl-2-oxopropyl]amino}carbonyl)pyrrolidinyl]carbonyl}propyl)amino]-2-oxoethyl}-2-oxo-1-imidazolidinyl)acetate | C27H42F3N5O7 | 详情 | 详情 | |
| (XII) | 36228 | 2-imidazolidinone | 120-93-4 | C3H6N2O | 详情 | 详情 |
| (XIII) | 17430 | 2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate | 5292-43-3 | C6H11BrO2 | 详情 | 详情 |
| (XIV) | 55788 | tert-butyl 2-{3-[2-(tert-butoxy)-2-oxoethyl]-2-oxo-1-imidazolidinyl}acetate | C15H26N2O5 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(I)Benclonidine has been synthesized by various routes: 1) Condensation of 1-benzoylimidazolidin-2-one (II) [obtained by reaction of imidazolidin-2-one (I) with benzoyl chloride (A)] and 2,6-dichloroaniline (III) in the presence of phosphoroxy chloride at elevated temperature yields title compound. (1) 2) Clonidine (IV) reacts with benzoylimidazole (V) in aprotic solvents to give directly benclonidine. (2) 3) 2,6-Dichlorophenylisocyanide dichloride (VI) and benzoylethylenediamine (VII) are condensed in the presence of an acid acceptor to give benclonidine. (2)
| 【1】 Franzmair, R.; Pittner, H. (Chemie Linz AG); AU 333749 . |
| 【2】 Franzmair, R. (Chemie Linz AG); AU 339897 . |
| 【3】 Koch, H.; Benclonidine. Drugs Fut 1984, 9, 6, 408. |
| 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) | 10463 | Benzoyl chloride | 98-88-4 | C7H5ClO | 详情 | 详情 |
| (I) | 36228 | 2-imidazolidinone | 120-93-4 | C3H6N2O | 详情 | 详情 |
| (II) | 60764 | 1-benzoyl-2-imidazolidinone | C10H10N2O2 | 详情 | 详情 | |
| (III) | 60765 | 2,6-dichloroaniline; 2,6-dichlorophenylamine | C6H5Cl2N | 详情 | 详情 | |
| (IV) | 60767 | 2,6-dichloro-N-(2-imidazolidinylidene)aniline; N-(2,6-dichlorophenyl)-N-(2-imidazolidinylidene)amine | C9H9Cl2N3 | 详情 | 详情 | |
| (V) | 60766 | 1H-imidazol-1-yl(phenyl)methanone | C10H8N2O | 详情 | 详情 | |
| (VI) | 60768 | 1,3-dichloro-2-[(dichloromethylene)amino]benzene | C7H3Cl4N | 详情 | 详情 | |
| (VII) | 60769 | N-(2-aminoethyl)benzamide | C9H12N2O | 详情 | 详情 |