3,4-dimethoxy-3-cyclobutene-1,2-dione -Drug Synthesis Database

【结构式】

【分子编号】19999

【品名】3,4-dimethoxy-3-cyclobutene-1,2-dione

【CA登记号】5222-73-1

【分子式】C₆H₆O₄

【分子量】142.11124

【元素组成】C 50.71% H 4.26% O 45.03%

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：(III)

The metalation of 4-chlorobromobenzene (I) with lithium gives 4-chlorophenyllithium (II), which is condensed with dimethyl squarate (III) in THF at -78 C giving 4-(4-chlorophenyl)-4-hydroxy-2,3-dimethoxy-2-cyclobuten-1-one (IV). The isomerization of (IV) in refluxing xylene (38 C) affords naphthohydroquinone (VI) through the intermediate ketene (V). Finally, compound (VI) is acetylated with acetic anhydride in pyridine - dimethylaminopyridine.

参考文献中间体

合成目标

【1】 Perri, S.T.; Moore, H.W.; Synthesis of lonapalene. Tetrahedron Lett 1987, 28, 39, 4507-10.

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)	14733	4-Bromochlorobenzene; 1-bromo-4-chlorobenzene	106-39-8	C₆H₄BrCl	详情	详情
(II)	19396	(4-chlorophenyl)lithium		C₆H₄ClLi	详情	详情
(III)	19999	3,4-dimethoxy-3-cyclobutene-1,2-dione	5222-73-1	C₆H₆O₄	详情	详情
(IV)	20000	4-(4-chlorophenyl)-4-hydroxy-2,3-dimethoxy-2-cyclobuten-1-one		C₁₂H₁₁ClO₄	详情	详情
(V)	20001	(3Z)-4-(4-chlorophenyl)-4-hydroxy-2,3-dimethoxy-1,3-butadien-1-one		C₁₂H₁₁ClO₄	详情	详情
(VI)	20002	6-chloro-2,3-dimethoxy-1,4-naphthalenediol		C₁₂H₁₁ClO₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The condensation of 4-amino-2(Z)-buten-1-ol (I) with 2-bromo-4-(piperidinomethyl)pyridine (II) by means of NaH in refluxing THF gives 4-[4-(piperidinomethyl)pyridin-2-yloxy]-2(Z)-butenylamine (III), which is allowed to react with 3,4,-dimethoxy-3-cyclobutene-1,2-dione (IV) in methanol to afford 3-methoxy-4-[4-[4-(piperidinomethyl)pyridin-2-yloxy]-2(Z)-butenylamino]-3-cyclobutene-1,2-dione (V). Finally, this compound is treated with dry ammonia in methanol.

参考文献中间体

合成目标

【1】 Nohara, F.; Fujinawa, T. (Ikeda Mohando); Pyridyloxy derivs.. AU 8548136; EP 0177016; ES 8701161; JP 1986085365; JP 1986207375; JP 1991261766; US 4710498 .
【2】 Prous, J.; Castaner, J.; IT-066. Drugs Fut 1990, 15, 12, 1181.

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)	13022	(Z)-4-Amino-2-buten-1-ol		C₄H₉NO	详情	详情
(II)	13021	2-Bromo-4-(1-piperidinylmethyl)pyridine		C₁₁H₁₅BrN₂	详情	详情
(III)	13023	(Z)-4-[[4-(1-Piperidinylmethyl)-2-pyridinyl]oxy]-2-buten-1-amine; (Z)-4-[[4-(1-Piperidinylmethyl)-2-pyridinyl]oxy]-2-butenylamine		C₁₅H₂₃N₃O	详情	详情
(IV)	19999	3,4-dimethoxy-3-cyclobutene-1,2-dione	5222-73-1	C₆H₆O₄	详情	详情
(V)	31233	3-methoxy-4-[((Z)-4-[[4-(1-piperidinylmethyl)-2-pyridinyl]oxy]-2-butenyl)amino]-3-cyclobutene-1,2-dione		C₂₀H₂₅N₃O₄	详情	详情

Extended Information