3-[3-(benzyloxy)propoxy]-5-methylphenyl 2-chlorobenzenesulfonate -Drug Synthesis Database

【结构式】

【分子编号】30819

【品名】3-[3-(benzyloxy)propoxy]-5-methylphenyl 2-chlorobenzenesulfonate

【CA登记号】

【分子式】C₂₃H₂₃ClO₅S

【分子量】446.95132

【元素组成】C 61.81% H 5.19% Cl 7.93% O 17.9% S 7.17%

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)

Orcinol (I) is first derivatized to (III) by reaction with sulfonyl chloride (II) in a mixture of aqueous NaHCO3 (sat) and Et2O. Monosulfonate (III) undergoes Mitsunobu reaction with monobenzylated diol (IV) in the presence of PPh3 and DEAD in dichloromethane to yield derivative (V), which is then debenzylated by hydrogenolysis over Pd/C in MeOH, or in THF/HCl/dioxane, to afford (VI). Alcohol (VI) is oxidized with SO3·pyr complex in DMSO/dichloromethane in the presence of DIEA to provide aldehyde (VIII), which finally reacts with aminoguanidine nitrate in EtOH in the presence of HCl/dioxane.

参考文献中间体

合成目标

【1】 Soll, R.M.; Lu, T.; Tomczuk, B.; et al.; Amidinohydrazones as guanidine bioisosteres: Application to a new class of potent, selective and orally bioavailable, non-amide-based small-molecule thrombin inhibitors. Bioorg Med Chem Lett 2000, 10, 1, 1.
【2】 Soll, R.M.; Lu, T.; Fedde, C.L.; Tomczuk, B.E.; Illig, C. (3-Dimensional Pharmaceuticals, Inc.); Amidinohydrazones as protease inhibitors. EP 0906091; JP 2000507588; US 5891909; WO 9736580 .

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)	14687	3-(benzyloxy)-1-propanol; 3-(Benzyloxy)propanol	4799-68-2	C₁₀H₁₄O₂	详情	详情
(V)	30819	3-[3-(benzyloxy)propoxy]-5-methylphenyl 2-chlorobenzenesulfonate		C₂₃H₂₃ClO₅S	详情	详情
(VI)	30820	3-(3-hydroxypropoxy)-5-methylphenyl 2-chlorobenzenesulfonate		C₁₆H₁₇ClO₅S	详情	详情
(VII)	30821	3-methyl-5-(3-oxopropoxy)phenyl 2-chlorobenzenesulfonate		C₁₆H₁₅ClO₅S	详情	详情
(VIII)	10015	1-Hydrazinecarboximidamide; Hydrazinecarboximidamide	79-17-4	CH₆N₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

2-Chlorobenzenesulfonyl chloride (I) was coupled to orcinol (II) to give sulfonate (III). Subsequent condensation of (III) with 3-benzyloxypropanol (IV) under Mitsunobu conditions afforded ether (V). After hydrogenolytic deprotection of the benzyl group, Swern oxidation of the resulting alcohol (VI) with DMSO and SO3-pyridine complex provided aldehyde (VII). The title amidinohydrazone was then obtained by treatment of (VII) with aminoguanidine nitrate (VIII).

参考文献中间体

合成目标

【1】 Soll, R.M.; Lu, T.; Fedde, C.L.; Tomczuk, B.E.; Illig, C. (3-Dimensional Pharmaceuticals, Inc.); Amidinohydrazones as protease inhibitors. EP 0906091; JP 2000507588; US 5891909; WO 9736580 .
【2】 Tomczuk, B.E.; Stagnaro, T.P.; Fedde, C.L.; Lu, T.; Markotan, T.P.; Illig, C.R.; Soll, R.M. (3-Dimensional Pharmaceuticals, Inc.); Aminoguanidines and alkoxyguanidines as protease inhibitors. EP 0944590; WO 9823565 .

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)	30817	2-chlorobenzenesulfonyl chloride	2905-23-9	C₆H₄Cl₂O₂S	详情	详情
(II)	27257	5-Methyl-1,3-benzenediol; Orcinol	505-15-4	C₇H₈O₂	详情	详情
(III)	30818	3-hydroxy-5-methylphenyl 2-chlorobenzenesulfonate		C₁₃H₁₁ClO₄S	详情	详情
(IV)	14687	3-(benzyloxy)-1-propanol; 3-(Benzyloxy)propanol	4799-68-2	C₁₀H₁₄O₂	详情	详情
(V)	30819	3-[3-(benzyloxy)propoxy]-5-methylphenyl 2-chlorobenzenesulfonate		C₂₃H₂₃ClO₅S	详情	详情
(VI)	30820	3-(3-hydroxypropoxy)-5-methylphenyl 2-chlorobenzenesulfonate		C₁₆H₁₇ClO₅S	详情	详情
(VII)	30821	3-methyl-5-(3-oxopropoxy)phenyl 2-chlorobenzenesulfonate		C₁₆H₁₅ClO₅S	详情	详情
(VIII)	10015	1-Hydrazinecarboximidamide; Hydrazinecarboximidamide	79-17-4	CH₆N₄	详情	详情

Extended Information