N-(4-aminophenyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,4-benzenediamine -Drug Synthesis Database

【结构式】

【分子编号】35075

【品名】N-(4-aminophenyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,4-benzenediamine

【CA登记号】6219-73-4

【分子式】C₈H₁₂N₂

【分子量】136.19676

【元素组成】C 70.55% H 8.88% N 20.57%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XI)

Condensation of 1,2,4-benzenetricarboxylic anhydride (X) with N,N-dimethyl-p-phenylenediamine (XI) in boiling AcOH produced phthalimide (XII). The title amide was then obtained by coupling of acid (XII) with amine (IV) in the presence of HATU, or EDC, HOBt and DMAP in dichloromethane.

参考文献中间体

合成目标

【1】 Prouty, C.; Wang, J.; Kuo, G.-H.; Pulito, V.; Murray, W.V.; Cheung, P.; Jolliffe, L.; Varga, S.; Evangelisto, M.; Design, synthesis, and structure-activity relationships of phthalimide-phenylpiperazines: A novel series of potent and selective alpha1a-adrenergic receptor antagonists. J Med Chem 2000, 43, 11, 2183.
【2】 Murray, W.V.; Kuo, G.-H.; Prouty, C.P. (Ortho-McNeil Pharmaceutical, Inc.); Phthalimido arylpiperazines as alpha 1a receptor antagonists useful in the treatment of benign prostatic hyperplasia. US 6063785; WO 9942445 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	35069	(2S)-1-amino-3-[4-(2-isopropoxyphenyl)-1-piperazinyl]-2-propanol		C₁₆H₂₇N₃O₂	详情	详情
(X)	35074	1,3-dioxo-1,3-dihydro-2-benzofuran-5-carboxylic acid	552-30-7	C₉H₄O₅	详情	详情
(XI)	35075	N-(4-aminophenyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,4-benzenediamine	6219-73-4	C₈H₁₂N₂	详情	详情
(XII)	35076	2-[4-(dimethylamino)phenyl]-1,3-dioxo-5-isoindolinecarboxylic acid		C₁₇H₁₄N₂O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

Diphenylmethane (I) is nitrated to the tetranitro derivative (II) employing KNO3 in concentrated H2SO4. Oxidation of the diarylmethane (II) with CrO3 in boiling HOAc provides benzophenone (III). Cyclization of (III) under reductive conditions gives rise to the diamino acridone (IV), which is further acylated by 3-chloropropionyl chloride (V) to the bis-chloropropionamide (VI). Nucleophilic substitution of the chloride groups of (VI) with pyrrolidine (VII) furnishes the bis-pyrrolidino derivative (VIII). Chlorination of acridone (VIII) with POCl3 yields the chloroacridine (IX). This is finally condensed with 4-(dimethylamino)aniline (X) to produce the title compound.

参考文献中间体

合成目标

【1】 Read, M.; et al.; Structure-based design of selective and potent G quadruplex-mediated telomerase inhibitors. Proc Natl Acad Sci USA 2001, 98, 9, 4844.
【2】 Neidle, S.; Harrison, R.J.; Kelland, L.R.; Gowan, S.M.; Read, M.; Reszka, T. (Cancer Research Technology Ltd.); Therapeutic acridone and acridine cpds.. WO 0208193 .

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)	57799	Benzylbenzene; Benzylphenyl; Diphenylmethane; Ditane; Methylenedibenzene	101-81-5	C₁₃H₁₂	详情	详情
(II)	57800	bis(2,4-Dinitrophenyl)methane		C₁₃H₈N₄O₈	详情	详情
(III)	57801	bis(2,4-dinitrophenyl)methanone		C₁₃H₆N₄O₉	详情	详情
(IV)	57802	3,6-diamino-9(10H)-acridinone		C₁₃H₁₁N₃O	详情	详情
(V)	18936	3-chloropropanoyl chloride	625-36-5	C₃H₄Cl₂O	详情	详情
(VI)	57803	3-chloro-N-{6-[(3-chloropropanoyl)amino]-9-oxo-9,10-dihydro-3-acridinyl}propanamide		C₁₉H₁₇Cl₂N₃O₃	详情	详情
(VII)	11376	Pyrrolidine	123-75-1	C₄H₉N	详情	详情
(VIII)	57804	N-(9-oxo-6-{[3-(1-pyrrolidinyl)propanoyl]amino}-9,10-dihydro-3-acridinyl)-3-(1-pyrrolidinyl)propanamide		C₂₇H₃₃N₅O₃	详情	详情
(IX)	57805	N-(9-chloro-6-{[3-(1-pyrrolidinyl)propanoyl]amino}-3-acridinyl)-3-(1-pyrrolidinyl)propanamide		C₂₇H₃₂ClN₅O₂	详情	详情
(X)	35075	N-(4-aminophenyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,4-benzenediamine	6219-73-4	C₈H₁₂N₂	详情	详情

Extended Information