(1S,5S,6R)-8-methyl-3-(4-methylphenyl)-6-[(4-methylphenyl)sulfinyl]-8-azabicyclo[3.2.1]oct-3-en-2-one -Drug Synthesis Database

【结构式】

【分子编号】25802

【品名】(1S,5S,6R)-8-methyl-3-(4-methylphenyl)-6-[(4-methylphenyl)sulfinyl]-8-azabicyclo[3.2.1]oct-3-en-2-one

【CA登记号】

【分子式】C₂₂H₂₃NO₂S

【分子量】365.49616

【元素组成】C 72.3% H 6.34% N 3.83% O 8.75% S 8.77%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(III)

Dipolar cycloaddition of hydroxypyridinium betaine (I) with R-(+)-p-tolyl vinyl sulfoxide (II) furnished the chiral tropenone (III). Subsequent copper-catalyzed conjugate addition of phenyl-magnesium bromide on the beta-face of (III) provided the trans diaryltropanone (IV). Then, ketone reduction of (IV) with LiAlH4 gave alcohol (V), which was condensed with phenyl thionochloroformate (VI) to afford thiocarbonate (VII). This was reduced with tributyltin hydride and azobis(isobutyronitrile) to produce tropane (VIII). The sulfoxide group of (VIII) was further reduced to sulfide (IX) with PCl3 in DMF. Finally, Raney Nickel-promoted desulfurization in boiling EtOH yielded the title compound.

参考文献中间体

合成目标

【1】 Kozikowski, A.P.; Araldi, G.L.; Prakash, K.R.; Zhang, M.; Johnson, K.M.; Synthesis and biological properties of new 2beta-alkyl- and 2beta-aryl-3-(substituted phenyl)tropane derivatives: Stereochemical effect of C-3 on affinity and selectivity for neuronal dopamine and serotonin transporters. J Med Chem 1998, 41, 25, 4973.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	17616	bromo(phenyl)magnesium; Phenyl Magnesium Bromide	100-58-3	C₆H₅BrMg	详情	详情
(I)	25800	1-methyl-4-(4-methylphenyl)-3-pyridiniumolate		C₁₃H₁₃NO	详情	详情
(II)	25801	(4-methylphenyl)(oxo)vinyl-lambda(4)-sulfane; 4-methylphenyl vinyl sulfoxide		C₉H₁₀OS	详情	详情
(III)	25802	(1S,5S,6R)-8-methyl-3-(4-methylphenyl)-6-[(4-methylphenyl)sulfinyl]-8-azabicyclo[3.2.1]oct-3-en-2-one		C₂₂H₂₃NO₂S	详情	详情
(IV)	25803	(1S,3R,4R,5S,6R)-8-methyl-3-(4-methylphenyl)-6-[(4-methylphenyl)sulfinyl]-4-phenyl-8-azabicyclo[3.2.1]octan-2-one		C₂₈H₂₉NO₂S	详情	详情
(V)	25804	(1S,3R,4R,5S,6R)-8-methyl-3-(4-methylphenyl)-6-[(4-methylphenyl)sulfinyl]-4-phenyl-8-azabicyclo[3.2.1]octan-2-ol		C₂₈H₃₁NO₂S	详情	详情
(VI)	25805	1-[(chlorocarbothioyl)oxy]benzene; Phenylchlorothioformate	1005-56-7	C₇H₅ClOS	详情	详情
(VII)	25806	O-[(1S,3R,4R,5S,6R)-8-methyl-3-(4-methylphenyl)-6-[(4-methylphenyl)sulfinyl]-4-phenyl-8-azabicyclo[3.2.1]oct-2-yl] O-phenyl carbonothioate		C₃₅H₃₅NO₃S₂	详情	详情
(VIII)	25807	(1R,3R,4R,5S,6R)-8-methyl-3-(4-methylphenyl)-4-phenyl-8-azabicyclo[3.2.1]oct-6-yl 4-methylphenyl sulfoxide; (1S,2R,3R,5R,7R)-8-methyl-3-(4-methylphenyl)-7-[(4-methylphenyl)sulfinyl]-2-phenyl-8-azabicyclo[3.2.1]octane		C₂₈H₃₁NOS	详情	详情
(IX)	25808	(1R,3R,4R,5S,6R)-8-methyl-3-(4-methylphenyl)-4-phenyl-8-azabicyclo[3.2.1]oct-6-yl 4-methylphenyl sulfide; (1S,2R,3R,5R,7R)-8-methyl-3-(4-methylphenyl)-7-[(4-methylphenyl)sulfanyl]-2-phenyl-8-azabicyclo[3.2.1]octane		C₂₈H₃₁NS	详情	详情

Extended Information