(3-chloro-4-methoxyphenyl)methanamine; 3-chloro-4-methoxybenzylamine -Drug Synthesis Database

【结构式】

【分子编号】51978

【品名】(3-chloro-4-methoxyphenyl)methanamine; 3-chloro-4-methoxybenzylamine

【CA登记号】

【分子式】C₈H₁₀ClNO

【分子量】171.62624

【元素组成】C 55.99% H 5.87% Cl 20.66% N 8.16% O 9.32%

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：(V)

The reaction of 4-aminophthalimide (I) with NaNO2/HCl and then with CuCl/KCN gives 4-cyanophthalimide (II), which is treated with hydrazone in ethanol, yielding 6-cyanophthalazine-2,3(1H,4H)-dione (III). The reaction of (III) with refluxing POCl3 affords 1,4-dichlorophthalazine-6-carbonitrile (IV), which is condensed with 3-chloro-4-methoxybenzylamine (V) by means of TEA in THF to provide the secondary amine (VI). Finally, this compound is condensed with 4-hydroxypiperidine (VII) by means of DIEA in N-methyl-2-pyrrolidone to furnish the target phthalazine.

参考文献中间体

合成目标

【1】 Watanabe, N.; Kabasawa, Y.; Takase, Y.; Ozaki, F.; Ishibashi, K.; Miyazaki, K.; Matsukura, M.; Souda, S.; Miyake, K.; Ishihara, H.; Kodama, K.; Adachi, H. (Eisai Co., Ltd.); Fused pyridazine cpd.. EP 0722936; JP 1996225541; US 6218392; WO 9605176 .
【2】 Takase, Y.; Adachi, H.; Watanabe, N.; et al.; 4-(3-Chloro-4-methoxybenzyl)aminophthalazines: Synthesis and inhibitory activity toward phosphodiesterase 5. J Med Chem 2000, 43, 13, 2523.

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)	51974	5-amino-1H-isoindole-1,3(2H)-dione		C₈H₆N₂O₂	详情	详情
(II)	51975	1,3-dioxo-5-isoindolinecarbonitrile		C₉H₄N₂O₂	详情	详情
(III)	51976	1,4-dioxo-1,2,3,4-tetrahydro-6-phthalazinecarbonitrile		C₉H₅N₃O₂	详情	详情
(IV)	51977	1,4-dichloro-6-phthalazinecarbonitrile		C₉H₃Cl₂N₃	详情	详情
(V)	51978	(3-chloro-4-methoxyphenyl)methanamine; 3-chloro-4-methoxybenzylamine		C₈H₁₀ClNO	详情	详情
(VI)	51979	1-chloro-4-[(3-chloro-4-methoxybenzyl)amino]-6-phthalazinecarbonitrile		C₁₇H₁₂Cl₂N₄O	详情	详情
(VII)	12076	4-Piperidinol; 4-Hydroxypiperidine	5382-16-1	C₅H₁₁NO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIII)

The intermediate benzylamine derivative (XIII) was prepared by chlorination of 4-methoxybenzylamine (XII) employing either chlorine in HOAc or sulfuryl chloride. The 9-chloro group of (XI) was finally displaced with amine (XII) by heating at 170 C in a pressure tube to furnish the target 6,9-disubstituted tricyclic compound.

参考文献中间体

合成目标

【1】 Kim, S.; Wang, Y.; Yu, G.; Macor, J.; Chung, H.-J.; Humora, M.; Katipally, K. (Bristol-Myers Squibb Co.); Fused pyridopyridazine inhibitors of cGMP phosphodiesterase. EP 1165521; JP 2002540102; US 6316438; WO 0056719 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XI)	58548	1-(9-chloro-3-ethyl-3H-pyrazolo[4',3':5,6]pyrido[3,4-d]pyridazin-6-yl)-N-methyl-1H-imidazole-4-carboxamide		C₁₅H₁₃ClN₈O	详情	详情
(XII)	15098	4-Methoxybenzylamine; (4-Methoxyphenyl)methanamine	2393-23-9	C₈H₁₁NO	详情	详情
(XIII)	51978	(3-chloro-4-methoxyphenyl)methanamine; 3-chloro-4-methoxybenzylamine		C₈H₁₀ClNO	详情	详情

Extended Information