6-(methylamino)-5,6,7,8-tetrahydro-1,2-naphthalenediol -Drug Synthesis Database

【结构式】

【分子编号】49435

【品名】6-(methylamino)-5,6,7,8-tetrahydro-1,2-naphthalenediol

【CA登记号】

【分子式】C₁₁H₁₅NO₂

【分子量】193.24564

【元素组成】C 68.37% H 7.82% N 7.25% O 16.56%

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)

Nolomirole is synthesized by acylation of (rac)-6-(methylamino)-5,6,7,8-tetrahydronaphthalene-1,2-diol, CHF-1024 (I) with isobutyryl chloride (II) in THF. Reductocondensation of 5,6-dimethoxy-2-tetralone (III) with methylamine (IV) by means of LiBH4 or NaBH4 gives N-(5,6-dimethoxy-1,2,3,4-tetrahydronaphthalen-2-yl)-N-methylamine (V), which is treated with 48% HBr at 110 C.

参考文献中间体

合成目标

【1】 Castaner, J.; Mealy, N.E.; Bayes, M.; Leeson, P.A.; Nolomirole Hydrochloride. Drugs Fut 2001, 26, 11, 1046.
【2】 Chiesi, P.; Villani, V. (Chiesi Farmaceutici SpA); 1,2,3,4-Tetrahydronaphthaline derivs., process for their preparation and pharmaceutical compsns. containing them. DE 3320936; GB 2123410 .

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)	49435	6-(methylamino)-5,6,7,8-tetrahydro-1,2-naphthalenediol		C₁₁H₁₅NO₂	详情	详情
(II)	14932	isobutyryl chloride; 2-methylpropanoyl chloride	79-30-1	C₄H₇ClO	详情	详情
(III)	37386	5,6-dimethoxy-3,4-dihydro-2(1H)-naphthalenone		C₁₂H₁₄O₃	详情	详情
(IV)	11021	Methanamine; Methylamine	74-89-5	CH₅N	详情	详情
(V)	37381	N-(5,6-dimethoxy-1,2,3,4-tetrahydro-2-naphthalenyl)-N-methylamine; 5,6-dimethoxy-N-methyl-1,2,3,4-tetrahydro-2-naphthalenamine		C₁₃H₁₉NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The condensation of 2,3-dimethoxybenzaldehyde (VI) with pyruvic acid (VII) by means of KOH in ethanol/water gives 4-(2,3-dimethoxyphenyl)-2-oxo-3-butenoic acid (VIII), which is reductocondensed with methylamine (IV) by means of H2 over Pd/C in ethanol/ acetic acid to yield 4-(2,3-dimethoxyphenyl)-2-methylamino)butyric acid (IX). Reaction of acid (IX) with benzyl chloroformate (X) and NaOH in water affords the carbamate (XI), which is treated with refluxing SOCl2 to provide 4-[2-(2,3-dimethoxyphenyl)ethyl]-3-methyloxazolidine-2,5-dione (XII). Reaction of oxazolidinone (XII) with AlCl3 in dichloromethane provides 5,6-dimethoxy-2-(methylamino)-1,2,3,4-tetrahydronaphthalen-1-one (XIII), which is reduced with H2 over Pd/C in ethanol containing some methanolic HCl in an autoclave at 80 C to yield N-(5,6-dimethoxy-1,2,3,4-tetrahydronaphthalen-2-yl)-N-methylamine (V). Finally, this compound is demethylated by treatment with AlCl3 in hot toluene. Alternatively, 5,6-dimethoxy-2-(methylamino)-1,2,3,4-tetrahydronaphthalen-1-one (XIII) can first be demethylated with 48% HBr to give 5,6-dihydroxy-2-(methylamino)-1,2,3,4-tetrahydronaphthalen-1-one (XIV), which is then reduced by means of H2 over Pd/C in an autoclave at 80 C.

参考文献中间体

合成目标

【1】 Castaner, J.; Mealy, N.E.; Bayes, M.; Leeson, P.A.; Nolomirole Hydrochloride. Drugs Fut 2001, 26, 11, 1046.
【2】 Servadio, V.; Ventura, P.; Amari, G.; Chiesi, P.; Del Canale, M.; De Fanti, R. (Chiesi Farmaceutici SpA); A process for the preparation of 5,6-dihydroxy-2-amino-1,2,3,4-tetrahydronaphthalene derivs.. WO 9529147 .

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)	49435	6-(methylamino)-5,6,7,8-tetrahydro-1,2-naphthalenediol		C₁₁H₁₅NO₂	详情	详情
(IV)	11021	Methanamine; Methylamine	74-89-5	CH₅N	详情	详情
(V)	37381	N-(5,6-dimethoxy-1,2,3,4-tetrahydro-2-naphthalenyl)-N-methylamine; 5,6-dimethoxy-N-methyl-1,2,3,4-tetrahydro-2-naphthalenamine		C₁₃H₁₉NO₂	详情	详情
(VI)	17615	2,3-Dimethoxybenzaldehyde	86-51-1	C₉H₁₀O₃	详情	详情
(VII)	24066	2-oxopropionic acid	127-17-3	C₃H₄O₃	详情	详情
(VIII)	37376	(E)-4-(2,3-dimethoxyphenyl)-2-oxo-3-butenoic acid		C₁₂H₁₂O₅	详情	详情
(IX)	37377	4-(2,3-dimethoxyphenyl)-2-(methylamino)butyric acid		C₁₃H₁₉NO₄	详情	详情
(X)	10101	Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene	501-53-1	C₈H₇ClO₂	详情	详情
(XI)	37378	2-[[(benzyloxy)carbonyl](methyl)amino]-4-(2,3-dimethoxyphenyl)butyric acid		C₂₁H₂₅NO₆	详情	详情
(XII)	37379	4-(2,3-dimethoxyphenethyl)-3-methyl-1,3-oxazolidine-2,5-dione		C₁₄H₁₇NO₅	详情	详情
(XIII)	37380	5,6-dimethoxy-2-(methylamino)-3,4-dihydro-1(2H)-naphthalenone		C₁₃H₁₇NO₃	详情	详情
(XIV)	37387	5,6-dihydroxy-2-(methylamino)-3,4-dihydro-1(2H)-naphthalenone		C₁₁H₁₃NO₃	详情	详情

Extended Information