2-bromo-4-isopropylaniline; 2-bromo-4-isopropylphenylamine -Drug Synthesis Database

【结构式】

【分子编号】23782

【品名】2-bromo-4-isopropylaniline; 2-bromo-4-isopropylphenylamine

【CA登记号】51605-97-1

【分子式】C₉H₁₂BrN

【分子量】214.10502

【元素组成】C 50.49% H 5.65% Br 37.32% N 6.54%

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：(II)

Condensation of 5-amino-4,6-dichloro-2-methylpyrimidine (I) and 2-bromo-4-isopropylaniline (II) in boiling ethoxyethanol gave diarylamine (III). Subsequent diazotization of (III) using NaNO2 and AcOH produced the triazolopyrimidine (IV), which was finally condensed with bis(2-methoxyethyl)amine (V) in the presence of Et3N in refluxing EtOH to provide the title compound.

参考文献中间体

合成目标

【1】 Wilde, R.G.; Curry, M.; Cheeseman, R.S.; Bakthavatchalam, R.; Gilligan, P.J.; Hobbs, F.W.; Rescinito, J.P.; Chorvat, R.J.; Cocuzza, A.J.; Beck, J.P.; Synthesis, corticotropin-releasing factor receptor. J Med Chem 1999, 42, 5, 833.

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)	23537	4,6-dichloro-2-methyl-5-pyrimidinamine; 4,6-dichloro-2-methyl-5-pyrimidinylamine		C₅H₅Cl₂N₃	详情	详情
(II)	23782	2-bromo-4-isopropylaniline; 2-bromo-4-isopropylphenylamine	51605-97-1	C₉H₁₂BrN	详情	详情
(III)	23783	N(4)-(2-bromo-4-isopropylphenyl)-6-chloro-2-methyl-4,5-pyrimidinediamine; N-(5-amino-6-chloro-2-methyl-4-pyrimidinyl)-N-(2-bromo-4-isopropylphenyl)amine		C₁₄H₁₆BrClN₄	详情	详情
(IV)	23784	3-(2-bromo-4-isopropylphenyl)-7-chloro-5-methyl-3H-[1,2,3]triazolo[4,5-d]pyrimidine		C₁₄H₁₃BrClN₅	详情	详情
(V)	23785	N,N-bis(2-methoxyethyl)amine; 2-methoxy-N-(2-methoxyethyl)-1-ethanamine	111-95-5	C₆H₁₅NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

4-Hydroxy-6-methyl-3-nitro-2-pyridone (I) was treated with phosphoryl chloride in boiling N,N-diethylaniline, and the resulting dichloropyridine (II) was condensed with n-butyl ethylamine (III) to afford a regioisomeric mixture of 4- (IV) and 2-amino (V) pyridines. After chromatographic separation, the desired isomer (IV) was coupled with 2-bromo-4-isopropylaniline (VI) at 140 C to provide (VII). Reduction of the nitro group of (VII) using sodium hydrosulfite and ammonia yielded diamine (VIII). Subsequent cyclization of (VIII) with phosgene in refluxing toluene gave imidazopyridinone (IX), which was finally N-methylated by means of CH3I and KOH in acetone.

参考文献中间体

合成目标

【1】 Beck, J.P.; et al.; Purin-8-ones as corticotropin-releasing hormone (CRH-R1) receptor antagonists. Bioorg Med Chem Lett 1999, 9, 7, 967.

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)	23337	4-hydroxy-6-methyl-3-nitro-2(1H)-pyridinone	4966-90-9	C₆H₆N₂O₄	详情	详情
(II)	26787	2,4-dichloro-6-methyl-3-nitropyridine		C₆H₄Cl₂N₂O₂	详情	详情
(III)	26788	N-butyl-N-ethylamine	13360-63-9	C₆H₁₅N	详情	详情
(IV)	26789	N-butyl-2-chloro-N-ethyl-6-methyl-3-nitro-4-pyridinamine		C₁₂H₁₈ClN₃O₂	详情	详情
(V)	26790	N-butyl-4-chloro-N-ethyl-6-methyl-3-nitro-2-pyridinamine		C₁₂H₁₈ClN₃O₂	详情	详情
(VI)	23782	2-bromo-4-isopropylaniline; 2-bromo-4-isopropylphenylamine	51605-97-1	C₉H₁₂BrN	详情	详情
(VII)	26791	N-[2-(2-bromo-4-isopropylanilino)-6-methyl-3-nitro-4-pyridinyl]-N-butyl-N-ethylamine		C₂₁H₂₉BrN₄O₂	详情	详情
(VIII)	26792	N-[3-amino-2-(2-bromo-4-isopropylanilino)-6-methyl-4-pyridinyl]-N-butyl-N-ethylamine		C₂₁H₃₁BrN₄	详情	详情
(IX)	26793	3-(2-bromo-4-isopropylphenyl)-7-[butyl(ethyl)amino]-5-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one		C₂₂H₂₉BrN₄O	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

Aniline (I) was converted to the isothiocyanate (II) using thiophosgene in DMF, and then treated with cyanoacetamide and sulfur to afford thiazolothione (III). Subsequent reaction of (III) with acetic anhydride generated the pyrimidine (IV), which was chlorinated with refluxing POCl3 to give (V). Finally, condensation of (V) with diethylamine in boiling acetone furnished the target compound.

参考文献中间体

合成目标

【1】 Beck, J.P.; et al.; Thiazolo[4,5-d]pyrimidine thiones and -ones as corticotropin-releasing hormone (CRH-R1) receptor antagonists. Bioorg Med Chem Lett 1999, 9, 8, 1185.

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)	23782	2-bromo-4-isopropylaniline; 2-bromo-4-isopropylphenylamine	51605-97-1	C₉H₁₂BrN	详情	详情
(II)	27728	2-bromo-4-isopropyl-1-isothiocyanatobenzene		C₁₀H₁₀BrNS	详情	详情
(III)	27729	4-amino-3-(2-bromo-4-isopropylphenyl)-2-thioxo-2,3-dihydro-1,3-thiazole-5-carboxamide		C₁₃H₁₄BrN₃OS₂	详情	详情
(IV)	27730	3-(2-bromo-4-isopropylphenyl)-5-methyl-2-thioxo-2,3-dihydro[1,3]thiazolo[4,5-d]pyrimidin-7(6H)-one		C₁₅H₁₄BrN₃OS₂	详情	详情
(V)	27731	3-(2-bromo-4-isopropylphenyl)-7-chloro-5-methyl[1,3]thiazolo[4,5-d]pyrimidine-2(3H)-thione		C₁₅H₁₃BrClN₃S₂	详情	详情

Extended Information