-Drug Synthesis Database

【结构式】

【药物名称】

【化学名称】2-Chlorobenzenesulfonic acid 3-(1-amidino-4-piperidinylmethoxy)-5-methylphenyl ester hydrochloride

【CA登记号】189338-86-1 (free base)

【分子式】C₂₀H₂₅Cl₂N₃O₄S

【分子量】474.40995

【开发单位】

【药理作用】　

合成路线1 合成路线2

合成路线1

The monosulfonation of orcinol (I) with 2-chlorobenzenesulfonyl chloride (II) in ethyl ether/aqueous NaHCO3 gives the monosulfonate (III), which is condensed with 4-(methanesulfonyloxymethyl)piperidine-1-carboxylic acid tert-butyl ester (IV) by means of NaH in DMF to yield the aryl ether (V). The deprotection of (V) with 4N HCl in dioxane affords the piperidine (VI), which is finally treated with amidinosulfonic acid (VII) and TEA in DMF. The 4-(methanesulfonyloxymethyl)piperidine-1-carboxylic acid tert-butyl ester (IV) has been obtained as follows: The reaction of piperidine-4-carboxylic acid (VIII) with Boc2O and NaHCO3 in dioxane/water gives the protected piperidine (IX), which is reduced at the carboxyl group by means of BH3/THF yielding the carbinol (X). Finally, this compound is mesylated with MsCl and TEA in dichloromethane to afford the target intermediate.

参考文献中间体

【1】 Soll, R.M.; Spurlino, J.; Murphy, L.; Lu, T.; Salemme, F.R.; Bone, R.; Illig, C.R.; Tomczuk, B.E.; Structure-activity and crystallographic analysis of a new class of non-amide-based thrombin inhibitor. Bioorg Med Chem Lett 2000, 10, 1, 79.
【2】 Zetter, B.R.; Smith, R. (Children's Medical Center Corp.); Treatment of human prostate cancer with spermine. WO 9711691 .

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)	27257	5-Methyl-1,3-benzenediol; Orcinol	505-15-4	C₇H₈O₂	详情	详情
(II)	30817	2-chlorobenzenesulfonyl chloride	2905-23-9	C₆H₄Cl₂O₂S	详情	详情
(III)	30818	3-hydroxy-5-methylphenyl 2-chlorobenzenesulfonate		C₁₃H₁₁ClO₄S	详情	详情
(IV)	40396	tert-butyl 4-([[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]methyl)-1-piperidinecarboxylate		C₁₄H₂₇NO₃S	详情	详情
(V)	40397	tert-butyl 4-[(3-[[(2-chlorophenyl)sulfonyl]oxy]-5-methylphenoxy)methyl]-1-piperidinecarboxylate		C₂₄H₃₀ClNO₆S	详情	详情
(VI)	40398	3-methyl-5-(4-piperidinylmethoxy)phenyl 2-chlorobenzenesulfonate		C₁₉H₂₂ClNO₄S	详情	详情
(VII)	15984	amino(imino)methanesulfonic acid		CH₄N₂O₃S	详情	详情
(VIII)	17402	4-nipecotic acid;piperidine-4-carboxylic acid;p-nipecotic acid; Isonipecotic acid; Hexahydroisonicotinic acid; 4-Piperidinecarboxylic acid	498-94-2	C₆H₁₁NO₂	详情	详情
(IX)	17404	1-(tert-butoxycarbonyl)-4-piperidinecarboxylic acid; 1-BOC-piperidine-4-carboxylic acid; N-Boc-isonipecotic acid	84358-13-4	C₁₁H₁₉NO₄	详情	详情
(X)	40399	tert-butyl 4-(hydroxymethyl)-1-piperidinecarboxylate		C₁₁H₂₁NO₃	详情	详情

合成路线2

Alternatively, the monosulfonate (III) can also be obtained as follows: The benzylation of orcinol (I) with benzyl bromide (IX) and NaH in DMF gives the monoether (X), which is sulfonated with 2-chlorobenzenesulfonyl chloride (II) and DIPEA in CH2Cl2 affording the protected sulfonate (XI). Finally, this compound is deprotected by hydro-genation with H2 over Pd/C in THF to furnish the target monosulfonate (III).

参考文献中间体

【1】 Zetter, B.R.; Smith, R. (Children's Medical Center Corp.); Treatment of human prostate cancer with spermine. WO 9711691 .

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)	27257	5-Methyl-1,3-benzenediol; Orcinol	505-15-4	C₇H₈O₂	详情	详情
(II)	30817	2-chlorobenzenesulfonyl chloride	2905-23-9	C₆H₄Cl₂O₂S	详情	详情
(III)	30818	3-hydroxy-5-methylphenyl 2-chlorobenzenesulfonate		C₁₃H₁₁ClO₄S	详情	详情
(IX)	12912	1-(Bromomethyl)benzene; Alpha-bromotoluene	100-39-0	C₇H₇Br	详情	详情
(X)	40400	3-(benzyloxy)-5-methylphenol		C₁₄H₁₄O₂	详情	详情
(XI)	40401	3-(benzyloxy)-5-methylphenyl 2-chlorobenzenesulfonate		C₂₀H₁₇ClO₄S	详情	详情

Extended Information