(2S)-6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromene-2-carboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】34833

【品名】(2S)-6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromene-2-carboxylic acid

【CA登记号】

【分子式】C₁₄H₁₈O₄

【分子量】250.29452

【元素组成】C 67.18% H 7.25% O 25.57%

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：(I)

(S)-6-Hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (I) was coupled to N-(4-nitrophenyl)piperazine (II) via activation with 1,1'-carbonyldiimidazole to furnish the corresponding amide (III). Subsequent hydrogenation of the nitro group of (III) over Pd/C provided aniline (IV). This was finally condensed with S-methyl-2-thiophenethiocarboxamide (V) to yield the title amidine.

参考文献中间体

合成目标

【1】 Chabrier de Lassauniere, P.-E.; Auguet, M.; Auvin, S.; Bigg, D. (SCRAS (Societé de Conseils de Recherches et d'Applications Scientifiques)); Novel 2-(iminomethyl)amino-phenyl derivs., preparation, application as medicines and pharmaceutical compsns. containing same. EP 0973763; WO 9842696 .

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)	34833	(2S)-6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromene-2-carboxylic acid		C₁₄H₁₈O₄	详情	详情
(II)	20299	1-(4-nitrophenyl)piperazine	6269-89-2	C₁₀H₁₃N₃O₂	详情	详情
(III)	34834	[(2S)-6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl][4-(4-nitrophenyl)-1-piperazinyl]methanone		C₂₄H₂₉N₃O₅	详情	详情
(IV)	34835	[4-(4-aminophenyl)-1-piperazinyl][(2S)-6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromen-2-yl]methanone		C₂₄H₃₁N₃O₃	详情	详情
(V)	34836	methyl 2-thiophenecarbimidothioate		C₆H₇NS₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

Acylation of urea derivative (I) with cyanoacetic acid (II) in HOAc in the presence of Ac2O yields derivative (III), which is then cyclized by treatment with NaOH to provide (IV). Nitrosation of (IV) with NaNO2 and HCl affords nitroso derivative (V), which is then hydrogenated over Pd/C in EtOH to furnish substituted pyrimidinedione (VI). Finally, (VI) is coupled to Trolox (VII) with N-ethyl-N'-[3-(dimethylamino)propyl]carbodiimide hydrochloride (EDC·HCl) and 1-hydroxybenzotriazole (HOBt) in DMF or with 4-(dimethylamino)pyridine (DMAP) and N-dicyclohexylcarbodiimide (DCC) in CH2Cl2 to yield the target compound.

参考文献中间体

合成目标

【2】 Isobe, Y.; Goto, Y.; Tobe, M.; Takahashi, O. (Japan Energy Corp.); Hydroquinone derivs. and their medicinal use. JP 1998147575; US 5821247 .
【1】 Matsui, J.; Tsuchiya, M.; Hayashi, H.; Goto, Y.; Hirota, K.; Obara, f.; Isobe, Y.; Tobe, M.; Synthesis and biological evaluation of CX-659S and its related compounds for their inhibitory effects on the delayed-type hypersensitivity reaction. Bioorg Med Chem 2000, 8, 8, 2037.

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)	44181	N-methyl-N'-phenylurea	1007-36-9	C₈H₁₀N₂O	详情	详情
(II)	12591	Cyanoacetic Acid; 2-Cyanoacetic acid	372-09-8	C₃H₃NO₂	详情	详情
(III)	44182	N-(2-cyanoacetyl)-N-methyl-N'-phenylurea		C₁₁H₁₁N₃O₂	详情	详情
(IV)	44183	6-amino-3-methyl-1-phenyl-2,4(1H,3H)-pyrimidinedione		C₁₁H₁₁N₃O₂	详情	详情
(V)	44184	6-amino-3-methyl-5-nitro-1-phenyl-2,4(1H,3H)-pyrimidinedione		C₁₁H₁₀N₄O₄	详情	详情
(VI)	44185	5,6-diamino-3-methyl-1-phenyl-2,4(1H,3H)-pyrimidinedione		C₁₁H₁₂N₄O₂	详情	详情
(VII)	34833	(2S)-6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromene-2-carboxylic acid		C₁₄H₁₈O₄	详情	详情

Extended Information