4-amino-5-chloro-2-methoxy-N-(4-piperidinyl)benzamide -Drug Synthesis Database

【结构式】

【分子编号】19957

【品名】4-amino-5-chloro-2-methoxy-N-(4-piperidinyl)benzamide

【CA登记号】

【分子式】C₁₃H₁₈ClN₃O₂

【分子量】283.75764

【元素组成】C 55.03% H 6.39% Cl 12.49% N 14.81% O 11.28%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(IV)

The condensation of 4-amino-5-chloro-2-methoxybenzoic acid (I) with 4-amino-1-(triphenylmethyl)piperidine (II) by means of ethyl chloroformate and triethylamine in THF gives the corresponding amide (III), which is deprotected with HCl in actone yielding 4-amino-5-chloro-2-methoxy-N-(4-piperidyl)benzamide (IV). The condensation of (IV) with ethyl bromoacetate (V) by means of K2CO3 in DMF affords the substituted acetate (VI), which is finally saponified with NaOH in methanol.

参考文献中间体

合成目标

【1】 Ito, Y.; Kato, H.; Yasuda, S.; Iwasaki, N.; Nishino, H.; Takeshita, M. (Hokuriku Seiyaku Co., Ltd.); Benzamide deriv.. EP 0640601; US 5395832; US 5500422; WO 9214705 .

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)	12419	4-Amino-5-chloro-2-methoxybenzoic acid	7206-70-4	C₈H₈ClNO₃	详情	详情
(II)	19955	1-trityl-4-piperidinylamine; 1-trityl-4-piperidinamine		C₂₄H₂₆N₂	详情	详情
(III)	19956	4-amino-5-chloro-2-methoxy-N-(1-trityl-4-piperidinyl)benzamide		C₃₂H₃₂ClN₃O₂	详情	详情
(IV)	19957	4-amino-5-chloro-2-methoxy-N-(4-piperidinyl)benzamide		C₁₃H₁₈ClN₃O₂	详情	详情
(V)	16640	Ethyl 2-bromoacetate; Ethyl bromoacetate	105-36-2	C₄H₇BrO₂	详情	详情
(VI)	19959	ethyl 2-[4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-1-piperidinyl]acetate		C₁₇H₂₄ClN₃O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

4-Amino-5-chloro-2-methoxybenzoic acid (I) was converted to the mixed anhydride (II) upon treatment with ethyl chloroformate and Et3N. Subsequent coupling of (II) with 4-amino-1-tritylpiperidine (III) afforded amide (IV). The trityl group of (IV) was then removed by acidic treatment to give piperidine (V). Finally, alkylation of (V) with butyl bromoacetate (VI) furnished the title compound.

参考文献中间体

合成目标

【1】 Ito, Y.; Kato, H.; Yasuda, S.; Iwasaki, N.; Nishino, H.; Takeshita, M. (Hokuriku Seiyaku Co., Ltd.); Benzamide deriv.. EP 0640601; US 5395832; US 5500422; WO 9214705 .

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)	12419	4-Amino-5-chloro-2-methoxybenzoic acid	7206-70-4	C₈H₈ClNO₃	详情	详情
(II)	29299	4-Amino-5-chloro-2-methoxybenzoic acid methoxycarbonyl anhydride		C₁₀H₁₀ClNO₅	详情	详情
(III)	19955	1-trityl-4-piperidinylamine; 1-trityl-4-piperidinamine		C₂₄H₂₆N₂	详情	详情
(IV)	19956	4-amino-5-chloro-2-methoxy-N-(1-trityl-4-piperidinyl)benzamide		C₃₂H₃₂ClN₃O₂	详情	详情
(V)	19957	4-amino-5-chloro-2-methoxy-N-(4-piperidinyl)benzamide		C₁₃H₁₈ClN₃O₂	详情	详情
(VI)	29300	butyl 2-bromoacetate		C₃₂H₃₂ClN₃O₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

Alkylation of the benzamido piperidine (I) with ethyl chloroacetate (II) provided the piperidine acetate ethyl ester (III), which was further hydrolyzed with NaOH to the corresponding carboxylic acid (IV). The title butyl ester was prepared by reaction of acid (IV) with n-butyl bromide in the presence of K2CO3.

参考文献中间体

合成目标

【1】 Sakaguchi, J.; et al.; Synthesis and gastrointestinal prokinetic activity of novel benzamide derivatives with amphoteric side chains. Chem Pharm Bull 2001, 49, 4, 424.

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)	19957	4-amino-5-chloro-2-methoxy-N-(4-piperidinyl)benzamide		C₁₃H₁₈ClN₃O₂	详情	详情
(II)	16640	Ethyl 2-bromoacetate; Ethyl bromoacetate	105-36-2	C₄H₇BrO₂	详情	详情
(III)	19959	ethyl 2-[4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-1-piperidinyl]acetate		C₁₇H₂₄ClN₃O₄	详情	详情
(IV)	56564	2-{4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-1-piperidinyl}acetic acid		C₁₅H₂₀ClN₃O₄	详情	详情

Extended Information