NSC-624548, HO-221, -Drug Synthesis Database

【结构式】

【药物名称】NSC-624548, HO-221

【化学名称】N-(2-Nitrobenzoyl)-N'-[4-(5-bromo-2-pyrimidinyloxy)-3-chlorophenyl]urea
　　　　　　N-[4-(5-Bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2-nitrobenzoyl)urea

【CA登记号】105128-93-6

【分子式】C₁₈H₁₁BrClN₅O₅

【分子量】492.67587

【开发单位】Mitsubishi Pharma (Originator)

【药理作用】ANTIINFECTIVE THERAPY, Antiviral Drugs, Oncolytic Drugs, Antimetabolites, Reverse Transcriptase Inhibitors

合成路线1 合成路线2 合成路线3

合成路线1

1) The condensation of 4-amino-2-chlorophenol (I) with 5 bromo-2-chloropyrimidine (II) by means of K2CO3 in hot DMSO gives 4-(5-bromo-2-pyrimidinyloxy)-3-chloroaniline (III), which is then condensed with 2-nitrobenzoyl isocyanate (IV) in dioxane.

参考文献中间体

【1】 Haga, T.; Kondo, N.; Koyanagi, T.; Nakajima, T.; Sugi, H.; Watanabe, M.; Yamada, N.; Yokoyama, K. (Ishihara Sangyo Kaisha, Ltd.); Benzoyl urea cpds., process for their production, . CH 671576; EP 0192235; FR 2577551; GB 2171695; US 4727077 .
【2】 Hoshi, A.; Prous, J.; Castaner, J.; HO-221. Drugs Fut 1988, 13, 9, 822.

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)	23256	2-Amino-4-chlorobenzoic acid; 4-Amino-2-chlorophenol	3964-52-1	C₆H₆ClNO	详情	详情
(II)	21054	5-bromo-2-chloropyrimidine		C₄H₂BrClN₂	详情	详情
(III)	23258	4-[(5-bromo-2-pyrimidinyl)oxy]-3-chlorophenylamine; 4-[(5-bromo-2-pyrimidinyl)oxy]-3-chloroaniline		C₁₀H₇BrClN₃O	详情	详情
(IV)	23259	2-nitrobenzoyl isocyanate		C₈H₄N₂O₄	详情	详情

合成路线2

2) The reaction of aniline (III) with phosgene in ethyl acetate gives 4-(5-bromo-2-pyrimidinyloxy)-3-chlorophenyl isocyanate (V), which is then condensed with 2-nitrobenzamide (VI) in refluxing toluene.

参考文献中间体

【1】 Haga, T.; Kondo, N.; Koyanagi, T.; Nakajima, T.; Sugi, H.; Watanabe, M.; Yamada, N.; Yokoyama, K. (Ishihara Sangyo Kaisha, Ltd.); Benzoyl urea cpds., process for their production, . CH 671576; EP 0192235; FR 2577551; GB 2171695; US 4727077 .
【2】 Hoshi, A.; Prous, J.; Castaner, J.; HO-221. Drugs Fut 1988, 13, 9, 822.

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)	23256	2-Amino-4-chlorobenzoic acid; 4-Amino-2-chlorophenol	3964-52-1	C₆H₆ClNO	详情	详情
(II)	21054	5-bromo-2-chloropyrimidine		C₄H₂BrClN₂	详情	详情
(III)	23258	4-[(5-bromo-2-pyrimidinyl)oxy]-3-chlorophenylamine; 4-[(5-bromo-2-pyrimidinyl)oxy]-3-chloroaniline		C₁₀H₇BrClN₃O	详情	详情
(V)	23261	4-[(5-bromo-2-pyrimidinyl)oxy]-3-chlorophenyl isocyanate; 5-bromo-2-(2-chloro-4-isocyanatophenoxy)pyrimidine		C₁₁H₅BrClN₃O₂	详情	详情
(VI)	23260	2-nitrobenzamide	610-15-1	C₇H₆N₂O₃	详情	详情

合成路线3

3) The reaction of aminophenol (I) with isocyanate (IV) in dioxane gives N-(2-nitrobenzoyl(-N'-(3-chloro-4-hydroxyphenyl)urea (VII), which is then condensed with pyrimidine (II) by means of KOH in hot DMSO.

参考文献中间体

【1】 Haga, T.; Kondo, N.; Koyanagi, T.; Nakajima, T.; Sugi, H.; Watanabe, M.; Yamada, N.; Yokoyama, K. (Ishihara Sangyo Kaisha, Ltd.); Benzoyl urea cpds., process for their production, . CH 671576; EP 0192235; FR 2577551; GB 2171695; US 4727077 .
【2】 Hoshi, A.; Prous, J.; Castaner, J.; HO-221. Drugs Fut 1988, 13, 9, 822.

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)	23256	2-Amino-4-chlorobenzoic acid; 4-Amino-2-chlorophenol	3964-52-1	C₆H₆ClNO	详情	详情
(II)	21054	5-bromo-2-chloropyrimidine		C₄H₂BrClN₂	详情	详情
(IV)	23259	2-nitrobenzoyl isocyanate		C₈H₄N₂O₄	详情	详情
(VII)	23262	N-(3-chloro-4-hydroxyphenyl)-N'-(2-nitrobenzoyl)urea		C₁₄H₁₀ClN₃O₅	详情	详情

Extended Information