4-(dimethylamino)benzoyl chloride -Drug Synthesis Database

【结构式】

【分子编号】39988

【品名】4-(dimethylamino)benzoyl chloride

【CA登记号】4755-50-4

【分子式】C₉H₁₀ClNO

【分子量】183.63724

【元素组成】C 58.87% H 5.49% Cl 19.31% N 7.63% O 8.71%

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)

Treatment of 4-(dimethylamino)benzoic acid (I) with thionyl chloride produced the corresponding acid chloride (II). Subsequent coupling of (II) with 4-tert-butyldimethylsilyloxy-N1-(4-methoxybenzoyl)-1,2-benzenediamine (III) yielded the bisamide (IV). Finally, desilylation of (IV) in the presence of HCl in aqueous THF afforded the title phenol compound.

参考文献中间体

合成目标

【1】 Herron, D.K.; et al.; 1,2-Dibenzamidobenzene inhibitors of human factor Xa. J Med Chem 2000, 43, 5, 859.
【2】 Antithrombotic agents. WO 9900121 .

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)	39987	4-(dimethylamino)benzoic acid	619-84-1	C₉H₁₁NO₂	详情	详情
(II)	39988	4-(dimethylamino)benzoyl chloride	4755-50-4	C₉H₁₀ClNO	详情	详情
(III)	39989	N-(2-amino-4-[[tert-butyl(dimethyl)silyl]oxy]phenyl)-4-methoxybenzamide		C₂₀H₂₈N₂O₃Si	详情	详情
(IV)	39990	N-[5-[[tert-butyl(dimethyl)silyl]oxy]-2-[(4-methoxybenzoyl)amino]phenyl]-4-(dimethylamino)benzamide		C₂₉H₃₇N₃O₄Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The title compound can be synthesized by two routes. Condensation of anthranilic acid (I) with acid chloride (II) provides benzooxazinone (III). Refluxing of (III) with amine (IV) in the presence of p-toluenesulfonic acid yields a mixture of the target quinazolinone and the uncyclized diamide (V), which can be cyclized to the title compound by heating in H2SO4/HOAc.

参考文献中间体

合成目标

【1】 Wang, S.; et al.; Studies on quinazolinones as dual inhibitors of Pgp and MRP1 in multidrug resistance. Bioorg Med Chem Lett 2002, 12, 4, 571.

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)	11661	2-Aminobenzoic acid;Anthranilic acid; o-Aminobenzoic acid	118-92-3	C₇H₇NO₂	详情	详情
(II)	39988	4-(dimethylamino)benzoyl chloride	4755-50-4	C₉H₁₀ClNO	详情	详情
(III)	57723	2-[4-(dimethylamino)phenyl]-4H-3,1-benzoxazin-4-one		C₁₆H₁₄N₂O₂	详情	详情
(IV)	57724	2-[6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]-1-ethanamine; 2-[6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]ethylamine		C₁₃H₂₀N₂O₂	详情	详情
(V)	57725	N-{2-[6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]ethyl}-2-{[4-(dimethylamino)benzoyl]amino}benzamide		C₂₉H₃₄N₄O₄	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

The anthranilic amide (I) is converted to the corresponding iminophosphorane (II) by treatment with triphenylphosphine, hexachloroethane and triethylamine. Subsequent condensation of (II) with acid chloride (III) gives rise to the desired quinazolinone.

参考文献中间体

合成目标

【1】 Wang, S.; et al.; Studies on quinazolinones as dual inhibitors of Pgp and MRP1 in multidrug resistance. Bioorg Med Chem Lett 2002, 12, 4, 571.

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)	57726	2-amino-N-{2-[6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]ethyl}benzamide		C₂₀H₂₅N₃O₃	详情	详情
(II)	57727	N-{2-[6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]ethyl}-2-[(triphenylphosphoranylidene)amino]benzamide		C₃₈H₃₈N₃O₃P	详情	详情
(III)	39988	4-(dimethylamino)benzoyl chloride	4755-50-4	C₉H₁₀ClNO	详情	详情

合成路线4

该中间体在本合成路线中的序号：(IV)

The reductocondensation of 3-amino-5-(chloromethyl)benzoic acid methyl ester (I) with 2-aminothiazol-5-ylisothiocyanate (II) by means of NaBH4 gives the thioether (III), which is condensed with 4-(dimethylamino)benzoyl chloride (IV) by means of pyridine in dichloromethane to yield the amide (V). The hydrolysis of the ester group of (V) with NaOH in methanol affords the corresponding carboxylic acid (VI), which is finally condensed with 1-acetylpiperazine (VII) by means of WSC, HATU and DIEA in THF to provide the target piperazide.

参考文献中间体

合成目标

【1】 Wityak, J.; Das, J.; Liu, C.; Lin, J.; Spergel, S.H.; Moquin, R.V.; Furch, J.A.; Doweiko, A.; Kanner, S.; Lin, T.-A.; Selective Emt inhibitors: Discovery and SAR of 2-amino-[(5-thiomethyl)aryl]thiazoles. 225th ACS Natl Meet (March 23 2003, New Orleans) 2003, Abst MEDI 257.

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)	64135	methyl 3-amino-5-(chloromethyl)benzoate		C₉H₁₀ClNO₂	详情	详情
(II)	64136	2-amino-1,3-thiazole-5-sulfenyl cyanide	23056-10-2	C₄H₃N₃S₂	详情	详情
(III)	64137	methyl 3-amino-5-{[(2-amino-1,3-thiazol-5-yl)sulfanyl]methyl}benzoate		C₁₂H₁₃N₃O₂S₂	详情	详情
(IV)	39988	4-(dimethylamino)benzoyl chloride	4755-50-4	C₉H₁₀ClNO	详情	详情
(V)	64138	methyl 3-amino-5-{[(2-{[4-(dimethylamino)benzoyl]amino}-1,3-thiazol-5-yl)sulfanyl]methyl}benzoate		C₂₁H₂₂N₄O₃S₂	详情	详情
(VI)	64139	3-amino-5-{[(2-{[4-(dimethylamino)benzoyl]amino}-1,3-thiazol-5-yl)sulfanyl]methyl}benzoic acid		C₂₀H₂₀N₄O₃S₂	详情	详情
(VII)	20674	N-Acetyl piperazine; 1-(1-piperazinyl)-1-ethanone	13889-98-0	C₆H₁₂N₂O	详情	详情

Extended Information