3,3-diphenyl-1-propanethiol; 3,3-diphenylpropylhydrosulfide -Drug Synthesis Database

【结构式】

【分子编号】30783

【品名】3,3-diphenyl-1-propanethiol; 3,3-diphenylpropylhydrosulfide

【CA登记号】

【分子式】C₁₅H₁₆S

【分子量】228.35804

【元素组成】C 78.9% H 7.06% S 14.04%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VI)

Acylation of L-proline methyl ester (I) with methoxalyl chloride (II) afforded oxamate (III), which was condensed with 1,1-dimethylpropyl magnesium chloride to produce ketoamide (IV). Hydrolysis of the methyl ester of (IV) with LiOH gave carboxylic acid (V). This was finally coupled with 3,3-diphenylpropyl mercaptan (VI) using DCC and dimethylaminopyridine to give the title thioether.

参考文献中间体

合成目标

【1】 Limburg, D.C.; et al.; Synthesis of thioester FKBP12 ligands and evaluation of their in vitro and in vivo nerve regenerative effects. 217th ACS Natl Meet (March 21 1999, Anaheim) 1999, Abst MEDI 237.
【2】 Hamilton, G.S.; Li, J.-H. (Guilford Pharmaceuticals Inc.); Heterocyclic thioesters and ketones. EP 0934263; US 5786378; US 5990131; WO 9813343 .
【3】 Hamilton, G.S.; Steiner, J.P. (Guilford Pharmaceuticals Inc.); Hair growth compsns. and uses. WO 9855090 .

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)	29552	methyl (2S)-2-pyrrolidinecarboxylate	2133-40-6	C₆H₁₁NO₂	详情	详情
(II)	26971	2-methoxy-2-oxoacetyl chloride	5781-53-3	C₃H₃ClO₃	详情	详情
(III)	30780	methyl (2S)-1-(2-methoxy-2-oxoacetyl)-2-pyrrolidinecarboxylate		C₉H₁₃NO₅	详情	详情
(IV)	30781	methyl (2S)-1-(3,3-dimethyl-2-oxopentanoyl)-2-pyrrolidinecarboxylate		C₁₃H₂₁NO₄	详情	详情
(V)	30782	(2S)-1-(3,3-dimethyl-2-oxopentanoyl)-2-pyrrolidinecarboxylic acid		C₁₂H₁₉NO₄	详情	详情
(VI)	30783	3,3-diphenyl-1-propanethiol; 3,3-diphenylpropylhydrosulfide		C₁₅H₁₆S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

3,3-Diphenyl-1-propanol (VII) is converted into the corresponding alkyl bromide (VIII) by treatment with CBr4 and PPh3. Reaction of bromide (VIII) with thiourea provides the isothiouronium salt (IX), which is further hydrolyzed to thiol (X) under alkaline conditions. Finally, acylation of thiol (X) with carboxylic acid (VI) by means of DCC yields the target thioester

参考文献中间体

合成目标

【1】 Hamilton, G.S.; Wu, Y.-Q.; Limburg, D.C.; Wilkinson, D.E.; Vaal ,M.J.; Li, J.-H.; Thomas, C.; Huang, W.; Sauer, H.; Ross, D.T.; Soni, R.; Chen, Y.; Guo, H.; Howorth, P.; Valentine, H.; Liang, S.; Spicer, D.; Fuller, M.; Steiner, J.P; Synthesis of N-glyoxyl prolyl and pipecolyl amides and thioesters and evaluation of their in vitro and in vivo nerve regenerative effects. J Med Chem 2002, 45, 16, 3549.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VI)	60290	1-(3,3-dimethyl-2-oxopentanoyl)-2-piperidinecarboxylic acid	C₁₃H₂₁NO₄	详情	详情
(VII)	60291	3,3-diphenyl-1-propanol	C₁₅H₁₆O	详情	详情
(VIII)	60292	1-(3-bromo-1-phenylpropyl)benzene	C₁₅H₁₅Br	详情	详情
(IX)	60293		C₁₆H₁₈N₂S	详情	详情
(X)	30783	3,3-diphenyl-1-propanethiol; 3,3-diphenylpropylhydrosulfide	C₁₅H₁₆S	详情	详情

Extended Information