5-bromo-2-chloropyrimidine -Drug Synthesis Database

【结构式】

【分子编号】21054

【品名】5-bromo-2-chloropyrimidine

【CA登记号】

【分子式】C₄H₂BrClN₂

【分子量】193.43006

【元素组成】C 24.84% H 1.04% Br 41.31% Cl 18.33% N 14.48%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(II)

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

合成目标

【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

该中间体在本合成路线中的序号：(II)

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

合成目标

【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

该中间体在本合成路线中的序号：(II)

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

合成目标

【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

合成路线4

该中间体在本合成路线中的序号：(X)

Ethyl phenylacetate (I) was alkylated with two equivalents of methyl iodide in the presence of potassium tert-butoxide to yield 2-methyl-2-phenylpropionic ester (II), which was reduced to alcohol (III) with LiAlH4. The alcohol function of (III) was esterified with Ac2O in pyridine, and the resulting compound (IV) was converted to sulfonyl chloride (V) by sulfonation with H2SO4, followed by treatment with SOCl2. Further reaction of (V) with ammonium hydroxide yielded sulfonamide (VI). Condensation of this sulfonamide with the dichloropyrimidine (VII) furnished, after saponification with NaOH, the N-pyrimidinylsulfonamide (VIII)). The alcohol function of (VIII) was then protected as the tetrahydropyranyl ether with dihydropyran and camphorsulfonic acid, and further treatment with the sodium salt of ethylene glycol at 100 C yielded the (2-hydroxyethoxy)pyrimidine (IX). Condensation of (IX) with 5-bromo-2-chloropyrimidine (X) in the presence of NaH gave (XI), which was finally converted to the target compound by acid deprotection of the tetrahydropyranyl acetal, followed by formation of the sodium salt with NaOMe in THF-MeOH.

参考文献中间体

合成目标

【1】 Yamada, K.; et al.; Syntheses and structure-activity relationships of sulfonamide derivatives as endothelin antagonists: A potent and selective ET-A antagonist, TA-0201 and related compounds. 216th ACS Natl Meet (Aug. 23-27, Boston) 1998, Abst MEDI 057.
【2】 Yamada, K.; Yasuda, K.; Kikkawa, K.; Kohno, R. (Tanabe Seiyaku Co., Ltd.); Benzenesulfonamide deriv. and process for preparing thereof. CA 2137953; EP 0658548; JP 1996099961; US 5589478; US 5728706 .

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)	21045	ethyl 2-phenylacetate	101-97-3	C₁₀H₁₂O₂	详情	详情
(II)	17609	ethyl 2-methyl-2-phenylpropanoate		C₁₂H₁₆O₂	详情	详情
(III)	17174	2-methyl-2-phenyl-1-propanol		C₁₀H₁₄O	详情	详情
(IV)	17175	2-methyl-2-phenylpropyl acetate	2901-13-5	C₁₂H₁₆O₂	详情	详情
(V)	21049	2-[4-(chlorosulfonyl)phenyl]-2-methylpropyl acetate		C₁₂H₁₅ClO₄S	详情	详情
(VI)	21050	2-[4-(aminosulfonyl)phenyl]-2-methylpropyl acetate		C₁₂H₁₇NO₄S	详情	详情
(VII)	21051	4,6-dichloro-5-(4-methylphenyl)pyrimidine		C₁₁H₈Cl₂N₂	详情	详情
(VIII)	21052	N-[6-chloro-5-(4-methylphenyl)-4-pyrimidinyl]-4-(2-hydroxy-1,1-dimethylethyl)benzenesulfonamide		C₂₁H₂₂ClN₃O₃S	详情	详情
(IX)	21053	4-[1,1-dimethyl-2-(tetrahydro-2H-pyran-2-yloxy)ethyl]-N-[6-(2-hydroxyethoxy)-5-(4-methylphenyl)-4-pyrimidinyl]benzenesulfonamide		C₂₈H₃₅N₃O₆S	详情	详情
(X)	21054	5-bromo-2-chloropyrimidine		C₄H₂BrClN₂	详情	详情
(XI)	21055	N-[6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-5-(4-methylphenyl)-4-pyrimidinyl]-4-[1,1-dimethyl-2-(tetrahydro-2H-pyran-2-yloxy)ethyl]benzenesulfonamide		C₃₂H₃₆BrN₅O₆S	详情	详情

Extended Information