WAY-132983, -Drug Synthesis Database

【结构式】

【药物名称】WAY-132983

【化学名称】(3R,4R)-3-[3-(Hexylsulfanyl)pyrazin-2-yloxy]-1-azabicyclo[2.2.1]heptane hydrochloride

【CA登记号】

【分子式】C₁₆H₂₆ClN₃OS

【分子量】343.92212

【开发单位】Wyeth Pharmaceuticals (Originator)

【药理作用】Cognition Disorders, Treatment of, NEUROLOGIC DRUGS, Muscarinic M1 Agonists

合成路线1

The reaction of 2,3-dichloropyrazine (I) with hexanethiol (II) by means of NaH in DMF/THF gives 2-chloro-3-(hexylsulfanyl)pyrazine (III), which is condensed with rac-exo-1-azabicyclo[2.2.1]heptan-3-ol (IV) by means of NaH in THF afforing the target compound as a racemic mixture that is submitted to optical resolution with tartaric acid. The intermediate -exo-1-azabicyclo[2.2.1]heptan-3-ol (IV) has been obtained as follows: The reduction of 1-azabicyclo[2.2.1]heptan-3-one (V) with H2 over PtO2in ethanol gives the corresponding endo-alcohol (VI), which is esterified under Mitsunobu conditions (PPh3, diisopropyl azodicarboxylate (DIAD) and benzoyl chloride) yielding the exo-benzoate (VII). The hydrolysis of (VII) with sodium methoxide in methanol affords the target exo-alcohol (IV).

参考文献中间体

【1】 Abou-Gharbia, M.; Tokolics, J.; Stein, P.; Moyer, J.A.; Husbands, G.M.; Tasse, R.P.; Sabb, A.L.; Boast, C.A.; Discovery of a highly potent, functionally-selective muscarinic M1 agonist, WAY-132983 using rational drug design and receptor modelling. Bioorg Med Chem Lett 1999, 9, 14, 1895.

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)	32326	2,3-dichloropyrazine	4858-85-9	C₄H₂Cl₂N₂	详情	详情
(II)	32327	hexylhydrosulfide; 1-hexanethiol	111-31-9	C₆H₁₄S	详情	详情
(III)	32328	2-chloro-3-(hexylsulfanyl)pyrazine; 3-chloro-2-pyrazinyl hexyl sulfide		C₁₀H₁₅ClN₂S	详情	详情
(IV)	32329	(3S,4R)-1-azabicyclo[2.2.1]heptan-3-ol		C₆H₁₁NO	详情	详情
(V)	32330	(4R)-1-azabicyclo[2.2.1]heptan-3-one		C₆H₉NO	详情	详情
(VI)	32331	(3R,4R)-1-azabicyclo[2.2.1]heptan-3-ol		C₆H₁₁NO	详情	详情
(VII)	32332	(3S,4R)-1-azabicyclo[2.2.1]hept-3-yl benzoate		C₁₃H₁₅NO₂	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)