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【结 构 式】 
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【分子编号】54583 【品名】(1-methyl-1H-pyrazol-5-yl)(phenyl)methanol; 5-(alpha-hydroxybenzyl)-1-methyl-1H-pyrazole 【CA登记号】 |
【 分 子 式 】C11H12N2O 【 分 子 量 】188.22916 【元素组成】C 70.19% H 6.43% N 14.88% O 8.5% |
合成路线1
该中间体在本合成路线中的序号：(rac)-(I)The key compound 5-(alpha-hydroxybenzyl)-1-methyl-1H-pyrazole [(±)-I] was obtained by two related ways: 1) by condensation of N-methylpyrazole with benzonitrile and butyl lithium in tetrahydrofuran and reduction of the obtained ketone with sodium borohydride in methanol or 2) by condensation of N-methylpyrazole with benzaldehyde and butyl lithium in THF/toluene. The alkylation of [(±)-I] with 2-(dimethylamino)ethyl chloride hydrochloride was carried out using phase transfer conditions and reaction with citric acid using propanone as solvent.
| 【1】 Farré, A.J.; Frigola, J.; Cizolirtine Citrate. Drugs Fut 2002, 27, 8, 721. |
| 【2】 Colombo, A.; Pares, J.; Frigola, J. (Laboratorios del Dr. Esteve, SA); Aryl-heteroaryl-carbinol derivs. having an analgesic activity. EP 0289380; FR 2613720; JP 1988267761; US 5017596 . |
合成路线2
该中间体在本合成路线中的序号：(rac)-(I)Resolution of alcohol [(±)-I] as its diastereomeric O-acetylmandelate esters and saponification of each of them in ethanol in the presence of catalytic amounts of sodium cyanide yielded the enantiomerically pure alcohols [(R)-(+)-I] and [(S)-()-I].
| 【1】 Hueso, J.; Frigola, J.; Farré, A.; Berrocal, J.; Gutierrez, B.; Preparation of the enantiomers of the analgesic E-3710. Bioorg Med Chem Lett 1993, 3, 2, 269. |
| 【2】 Farré, A.J.; Frigola, J.; Cizolirtine Citrate. Drugs Fut 2002, 27, 8, 721. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (rac)-(I) | 54583 | (1-methyl-1H-pyrazol-5-yl)(phenyl)methanol; 5-(alpha-hydroxybenzyl)-1-methyl-1H-pyrazole | C11H12N2O | 详情 | 详情 | |
| (R)-(+)-(I) | 54587 | (R)-(1-methyl-1H-pyrazol-5-yl)(phenyl)methanol | C11H12N2O | 详情 | 详情 | |
| (S)-(-)-(I) | 54588 | (S)-(1-methyl-1H-pyrazol-5-yl)(phenyl)methanol | C11H12N2O | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(rac)-(I)The transesterification of [(±)-I] with vinyl acetate enzymatically catalyzed (lipase) allowed the selective recovery of the enatiomer [(R)-(+)-I] and the hydrolysis and racemization of the undesired enantiomer [(S)-()-II] with hydrochloric acid.
| 【1】 Farré, A.J.; Frigola, J.; Cizolirtine Citrate. Drugs Fut 2002, 27, 8, 721. |
| 【2】 Frigola Constansa, J.; Cuberes Altisent, M.R.; Berrocal Romero, J.M.; Gotor Santamaria, V. (Laboratorios del Dr. Esteve, SA); Method for separating carbinols. ES 2128959; FR 2742147; US 5849931; WO 9720817 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (rac)-(I) | 54583 | (1-methyl-1H-pyrazol-5-yl)(phenyl)methanol; 5-(alpha-hydroxybenzyl)-1-methyl-1H-pyrazole | C11H12N2O | 详情 | 详情 | |
| (R)-(+)-(I) | 54587 | (R)-(1-methyl-1H-pyrazol-5-yl)(phenyl)methanol | C11H12N2O | 详情 | 详情 | |
| (S)-(-)-(III) | 54589 | (S)-(1-methyl-1H-pyrazol-5-yl)(phenyl)methyl acetate | C13H14N2O2 | 详情 | 详情 |