(R)-(1-methyl-1H-pyrazol-5-yl)(phenyl)methanol -Drug Synthesis Database

【结构式】

【分子编号】54587

【品名】(R)-(1-methyl-1H-pyrazol-5-yl)(phenyl)methanol

【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%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(R)-(+)-(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].

参考文献中间体

合成目标

【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	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2

该中间体在本合成路线中的序号：(R)-(+)-(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.

参考文献中间体

合成目标

【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	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

合成路线3

该中间体在本合成路线中的序号：(R)-(+)-(I)

Asymmetric reduction of ketone (III) with catecholborane or boranemethyl sulfide complex and CBS-oxazaborolidene as catalyst afforded [(R)-(+)-I] or [(S)-()-I].

参考文献中间体

合成目标

【1】 Farré, A.J.; Frigola, J.; Cizolirtine Citrate. Drugs Fut 2002, 27, 8, 721.
【2】 Frigola-Constansa, J.; Torrens-Jover, A. (Laboratorios del Dr. Esteve, SA); Process for obtaining enantiomers of cizolirtine. EP 1029852; ES 2130083; US 6118009; WO 9907684 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	20631	(R)-Methyl oxazaborolidine; (3aR)-1-methyl-3,3-diphenyltetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaborole	112022-83-0	C₁₈H₂₀BNO	详情	详情
(R)-(+)-(I)	54587	(R)-(1-methyl-1H-pyrazol-5-yl)(phenyl)methanol		C₁₁H₁₂N₂O	详情	详情
(III)	54590	(1-methyl-1H-pyrazol-5-yl)(phenyl)methanone		C₁₁H₁₀N₂O	详情	详情

合成路线4

该中间体在本合成路线中的序号：(R)-(+)-(I)

Ethyl (R)-mandelate [(R)-IV] was protected as its tert-butyldimethylsilyl ether and reduced with DIBAL to [(R)-V], which was treated with ethoxycarbonylmethyl-enetriphenylphosphorane, followed by reduction to give [(R)-VI]. Subsequent oxidation to [(R)-VII] and cyclization by reaction with methylhydrazine afforded a mixture of pyrazolines [(R)-VIII]. Oxidation to pyrazole and deprotection yielded [(R)-(+)-I].

参考文献中间体

合成目标

【1】 Farré, A.J.; Frigola, J.; Cizolirtine Citrate. Drugs Fut 2002, 27, 8, 721.
【2】 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.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(R)-(+)-(I)	54587	(R)-(1-methyl-1H-pyrazol-5-yl)(phenyl)methanol	C₁₁H₁₂N₂O	详情	详情
(R)-(IV)	54591	ethyl (2R)-2-hydroxy-2-phenylethanoate	C₁₀H₁₂O₃	详情	详情
(R)-(V)	54592	(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-phenylethanal	C₁₄H₂₂O₂Si	详情	详情
(R)-(VI)	54593	(E,4S)-4-{[tert-butyl(dimethyl)silyl]oxy}-4-phenyl-2-buten-1-ol	C₁₆H₂₆O₂Si	详情	详情
(R)-(VII)	54594	(E,4S)-4-{[tert-butyl(dimethyl)silyl]oxy}-4-phenyl-2-butenal	C₁₆H₂₄O₂Si	详情	详情
(R)-(VIII)	54595	tert-butyl(dimethyl)silyl (R)-(1-methyl-4,5-dihydro-1H-pyrazol-5-yl)(phenyl)methyl ether; 5-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]-1-methyl-4,5-dihydro-1H-pyrazole	C₁₇H₂₈N₂OSi	详情	详情

Extended Information