tert-butyl 4-(phenylsulfanyl)-1-piperidinecarboxylate -Drug Synthesis Database

【结构式】

【分子编号】32561

【品名】tert-butyl 4-(phenylsulfanyl)-1-piperidinecarboxylate

【CA登记号】

【分子式】C₁₆H₂₃NO₂S

【分子量】293.43016

【元素组成】C 65.49% H 7.9% N 4.77% O 10.91% S 10.93%

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：(III)

4-Hydroxypiperidine (I) was protected as the tert-butyl carbamate (II) upon treatment with (Boc)2O. Subsequent Mitsunobu coupling of (II) with diphenyl disulfide using tributylphosphine and diethyl azodicarboxylate afforded thioether (III). Acid deprotection of the Boc group of (III), followed by nitrosation of the resulting amine (IV) gave N-nitrosopiperidine (V). Further reduction of (V) with LiAlH4 yielded hydrazine (VI). Condensation of (VI) with dichloropurine derivative (VII) produced piperidinyladenosine (VIII). Debenzoylation of the tribenzoate ester (VIII) with methanolic ammonia gave (IX). Then, chlorination at position 5' with concomitant formation of the 2',3' cyclic sulfite (X) by reaction with thionyl chloride and pyridine was followed by sulfite hydrolysis with methanolic ammonia to yield the title compound.

参考文献中间体

合成目标

【1】 Lau, J.; Judge, M.E.; Sheardown, M.J.; Petersen, H.; Shalmi, M.; Knutsen, L.J.S.; Hansen, A.J.; Thomsen, C.; Weis, J.U.; N-substituted adenosines as novel neuroprotective A1 agonists with diminished hypotensive effects. J Med Chem 1999, 42, 18, 3463.
【2】 Lau, J.; Knutsen, L.J.S. (Novo Nordisk A/S); Chemical cpds., their preparation and use. EP 0719275; JP 1999511436; US 5589467; WO 9507921 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	17473	diphenyl disulfide; 1-(phenyldisulfanyl)benzene; diphenyldisulfide	882-33-7	C₁₂H₁₀S₂	详情	详情
(I)	12076	4-Piperidinol; 4-Hydroxypiperidine	5382-16-1	C₅H₁₁NO	详情	详情
(II)	18625	tert-butyl 4-hydroxy-1-piperidinecarboxylate		C₁₀H₁₉NO₃	详情	详情
(III)	32561	tert-butyl 4-(phenylsulfanyl)-1-piperidinecarboxylate		C₁₆H₂₃NO₂S	详情	详情
(IV)	32562	4-(phenylsulfanyl)piperidine; phenyl 4-piperidinyl sulfide		C₁₁H₁₅NS	详情	详情
(V)	32563	1-nitroso-4-piperidinyl phenyl sulfide; 1-nitroso-4-(phenylsulfanyl)piperidine		C₁₁H₁₄N₂OS	详情	详情
(VI)	32564	4-(phenylsulfanyl)-1-piperidinamine; 4-(phenylsulfanyl)-1-piperidinylamine		C₁₁H₁₆N₂S	详情	详情
(VII)	32565	(2R,3R,4R,5R)-4-(benzoyloxy)-2-[(benzoyloxy)methyl]-5-(2,6-dichloro-9H-purin-9-yl)tetrahydro-3-furanyl benzoate		C₃₁H₂₂Cl₂N₄O₇	详情	详情
(VIII)	32568	[(2R,3R,4R,5R)-3,4-bis(benzoyloxy)-5-(2-chloro-6-[[4-(phenylsulfanyl)-1-piperidinyl]amino]-9H-purin-9-yl)tetrahydro-2-furanyl]methyl benzoate		C₄₂H₃₇ClN₆O₇S	详情	详情
(IX)	32566	(2R,3R,4S,5R)-2-(2-chloro-6-[[4-(phenylsulfanyl)-1-piperidinyl]amino]-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol		C₂₁H₂₅ClN₆O₄S	详情	详情
(X)	32567	(3aR,4S,6R,6aR)-4-(chloromethyl)-6-(2-chloro-6-[[4-(phenylsulfanyl)-1-piperidinyl]amino]-9H-purin-9-yl)tetrahydro-2lambda(4)-furo[3,4-d][1,3,2]dioxathiol-2-one		C₂₁H₂₂Cl₂N₆O₄S₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The (phenylsulfanyl)piperidine (III) was obtained by condensation of N-Boc-4-piperidinol (I) with diphenyl disulfide (II) in the presence of tributylphosphine. Subsequent oxidation of sulfide (III) to the corresponding sulfone (IV) was achieved using oxone® on wet alumina. Deprotection of the N-Boc-piperidine (IV) with HCl afforded piperidine (V), which was finally alkylated with 2-bromo-4'-fluoroacetophenone (VI) to furnish the title N-phenacyl piperidine.

参考文献中间体

合成目标

【1】 Blurton, P.; Burkamp, F.; Fletcher, S.R.; et al.; 4-(Phenylsulfonyl)piperidines: Novel, selective, and biovailable 5-HT2A receptor antagonists. J Med Chem 2002, 45, 2, 492.
【2】 Macleod, A.M.; Blurton, P.; Fletcher, S.R.; Van Niel, M.B.; Burkamp, F.; Cheng, S.K.-F. (Merck Sharp & Dohme Ltd.); Phenylsulphonyl derivs. as 5-HT receptor ligands. EP 1147083; WO 0043362 .

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)	18625	tert-butyl 4-hydroxy-1-piperidinecarboxylate		C₁₀H₁₉NO₃	详情	详情
(II)	17473	diphenyl disulfide; 1-(phenyldisulfanyl)benzene; diphenyldisulfide	882-33-7	C₁₂H₁₀S₂	详情	详情
(III)	32561	tert-butyl 4-(phenylsulfanyl)-1-piperidinecarboxylate		C₁₆H₂₃NO₂S	详情	详情
(IV)	56311	tert-butyl 4-(phenylsulfonyl)-1-piperidinecarboxylate		C₁₆H₂₃NO₄S	详情	详情
(V)	56312	4-(phenylsulfonyl)piperidine; phenyl 4-piperidinyl sulfone		C₁₁H₁₅NO₂S	详情	详情
(VI)	27904	2-bromo-1-(4-fluorophenyl)-1-ethanone	403-29-2	C₈H₆BrFO	详情	详情

Extended Information