4-chloro-2-[(1-methyl-4-piperidinyl)sulfanyl]phenylamine; 4-chloro-2-[(1-methyl-4-piperidinyl)sulfanyl]aniline -Drug Synthesis Database

【结构式】

【分子编号】21791

【品名】4-chloro-2-[(1-methyl-4-piperidinyl)sulfanyl]phenylamine; 4-chloro-2-[(1-methyl-4-piperidinyl)sulfanyl]aniline

【CA登记号】

【分子式】C₁₂H₁₇ClN₂S

【分子量】256.79916

【元素组成】C 56.13% H 6.67% Cl 13.81% N 10.91% S 12.49%

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：(V)

Nucleophilic substitution of 2,4-dichloronitrobenzene (I) with 1-methylpiperidin-4-thiol (II) in the presence of K2CO3 provided a mixture of sulfides (III) and (IV), from which the major isomer (IV) was isolated by crystallization from EtOH. The nitro group of (IV) was then reduced with iron under acidic conditions to the corresponding amine (V). Subsequent diazotization of (V) and reduction of the diazonium salt (VI) with EtOH led to the deaminated compound (VII). N-Demethylation of (VII) was achieved by treatment with ethyl chloroformate, yielding the N-ethoxycarbonyl derivative (VIII). Finally, acid hydrolysis of carbamate (VIII) provided the target amine, which was isolated as the hydrochloride salt.

参考文献中间体

合成目标

【1】 Proska, J.; Radl, S.; Krejci, I.; Hezky, P.; Synthesis and analgesic activity of some deaza derivatives of anpirtoline. Arch Pharm 1999, 332, 1, 13.

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)	21787	2,4-dichloro-1-nitrobenzene	611-06-3	C₆H₃Cl₂NO₂	详情	详情
(II)	21788	1-methyl-4-piperidinethiol; 1-methyl-4-piperidinylhydrosulfide		C₆H₁₃NS	详情	详情
(III)	21789	4-[(3-chloro-4-nitrophenyl)sulfanyl]-1-methylpiperidine; 3-chloro-4-nitrophenyl 1-methyl-4-piperidinyl sulfide		C₁₂H₁₅ClN₂O₂S	详情	详情
(IV)	21790	4-[(5-chloro-2-nitrophenyl)sulfanyl]-1-methylpiperidine; 5-chloro-2-nitrophenyl 1-methyl-4-piperidinyl sulfide		C₁₂H₁₅ClN₂O₂S	详情	详情
(V)	21791	4-chloro-2-[(1-methyl-4-piperidinyl)sulfanyl]phenylamine; 4-chloro-2-[(1-methyl-4-piperidinyl)sulfanyl]aniline		C₁₂H₁₇ClN₂S	详情	详情
(VI)	21792	4-[[5-chloro-2-(1lambda(5)-diazynyl)phenyl]sulfanyl]-1-methylpiperidine; 5-chloro-2-(1lambda(5)-diazynyl)phenyl 1-methyl-4-piperidinyl sulfide		C₁₂H₁₆ClN₃S	详情	详情
(VII)	21793	4-[(3-chlorophenyl)sulfanyl]-1-methylpiperidine; 3-chlorophenyl 1-methyl-4-piperidinyl sulfide		C₁₂H₁₆ClNS	详情	详情
(VIII)	21794	ethyl 4-[(3-chlorophenyl)sulfanyl]-1-piperidinecarboxylate		C₁₄H₁₈ClNO₂S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

When 4-phenyl-3-oxobutanoic acid methyl ester (I) were reacted with thiourea (II), in the presence of sodium methoxide, condensation occurred with formation of 3,4-dihydro-6-benzyl-4-oxo-2-thioxopyrimidine (III). Reaction of the compound (III) with sec-butyl chloride (IV) in alkaline medium afforded the required 2-(sec-butylthio)-6-benzyl-3,4-dihydro-4-oxopyrimidine

参考文献中间体

合成目标

【1】 Artico, M.; Selected non-nucleoside reverse transcriptase inhibitors (NNRTIs): the DABOs family. Drugs Fut 2002, 27, 2, 159.

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)	21791	4-chloro-2-[(1-methyl-4-piperidinyl)sulfanyl]phenylamine; 4-chloro-2-[(1-methyl-4-piperidinyl)sulfanyl]aniline		C₁₂H₁₇ClN₂S	详情	详情
(II)	10180	Thiourea	62-56-6	CH₄N₂S	详情	详情
(III)	51793	6-benzyl-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone		C₁₁H₁₀N₂OS	详情	详情
(IV)	51797	1-methylpropyl chloride; 2-Chlorobutane; 1-Chloro-1-methylpropane; Sec-Butyl Chloride	78-86-4	C₄H₉Cl	详情	详情

Extended Information