3-[(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)amino]-1-propanol -Drug Synthesis Database

【结构式】

【分子编号】20960

【品名】3-[(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)amino]-1-propanol

【CA登记号】

【分子式】C₁₂H₁₇NO₃

【分子量】223.27192

【元素组成】C 64.55% H 7.67% N 6.27% O 21.5%

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)

Title compound can be prepared as shown in Scheme: 1) 3,6-Dichloropyridazine (I) is converted to 3(2H)-pyridazinone (III) in two steps. 2) 3-N-(2-Benzo[1,4]dioxanylmethyl)amino-1-propanol (V), obtained by the reaction of (2-benzo[1,4]dioxanylmethyl)-4-toluenesulfonate (IV) with 3-amino-1-propanol, is N-benzylated to form the N-protected amino alcohol (VI), which on treatment with thionyl chloride affords the chloroalkyl derivative (VII). 3) Alkylation of 3(2H)-pyridazinone (III) with (VII) under phase-transfer catalysis conditions to the N-benzylated GYKI-12743 (VIII) and then removal of the N-benzyl group by hydrogenation gives GYKI-12743.

参考文献中间体

合成目标

【1】 Kasztreiner, E.; Rabloczky, G.; Makk, N.; Jaszlits, L.; Matyus, P.; Cseh, G.; Pribusz, geb. Rapp, I.; Czakó, K.; Diesler, E.; Elekes, I.; Kaufer, L.; Kuhár, geb. Kürthy, M.; Kincsessy, J.; Kosáry, J.; Nagy, Gyöngyi geb. C. (Richter Gedeon Vegyeszeti); 3(2H)-Pyridazinone derivs., a process and intermediates for preparing them and medicaments containing them and/or other 3(2H)-pyridazinone derivatives. AU 8664496; EP 0220735; JP 87161768 .
【2】 Kasztreiner, E.; Matyus, P.; Rabloczky, G.; Jaszlits, L.; GYKI-12743. Drugs Fut 1989, 14, 7, 622.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	18522	3-amino-1-propanol	156-87-6	C₃H₉NO	详情	详情
	19171	1-(Chloromethyl)benzene; Benzyl chloride	100-44-7	C₇H₇Cl	详情	详情
(I)	11292	3,6-Dichloropyridazine	141-30-0	C₄H₂Cl₂N₂	详情	详情
(II)	20957	6-chloro-3(2H)-pyridazinone		C₄H₃ClN₂O	详情	详情
(III)	20958	3(2H)-pyridazinone		C₄H₄N₂O	详情	详情
(IV)	20959	2,3-dihydro-1,4-benzodioxin-2-ylmethyl 4-methylbenzenesulfonate		C₁₆H₁₆O₅S	详情	详情
(V)	20960	3-[(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)amino]-1-propanol		C₁₂H₁₇NO₃	详情	详情
(VI)	20961	3-[benzyl(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)amino]-1-propanol		C₁₉H₂₃NO₃	详情	详情
(VII)	20962	N-benzyl-3-chloro-N-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-1-propanamine; N-benzyl-N-(3-chloropropyl)-N-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)amine		C₁₉H₂₂ClNO₂	详情	详情
(VIII)	20963	2-[3-[benzyl(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)amino]propyl]-3(2H)-pyridazinone		C₂₃H₂₅N₃O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

The enantiomerically pure benzodioxane derivative (VIII) was obtained in a straightforward route including five steps starting from pyrocatechin (I). Racemic (VI) was then resolved by means of crystallization with (-)-O,O'-dibenzoyl-L-tartaric acid.

参考文献中间体

合成目标

【1】 Matyus, P.; GYKI-16084. Drugs Fut 1999, 24, 10, 1072.
【2】 3(2H)-Pyridazinone derivs. and pharmaceutical compsns. containing these cpds.. WO 9638441 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	18522	3-amino-1-propanol	156-87-6	C₃H₉NO	详情	详情
(I)	11599	o-Dihydroxybenzene; Catechol; Pyrocatechol	120-80-9	C₆H₆O₂	详情	详情
(II)	10146	Epichlorohydrin; 2-(Chloromethyl)oxirane	106-89-8	C₃H₅ClO	详情	详情
(III)	28714	2,3-dihydro-1,4-benzodioxin-2-ylmethanol	3663-82-9	C₉H₁₀O₃	详情	详情
(IV)	20959	2,3-dihydro-1,4-benzodioxin-2-ylmethyl 4-methylbenzenesulfonate		C₁₆H₁₆O₅S	详情	详情
(V)	20960	3-[(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)amino]-1-propanol		C₁₂H₁₇NO₃	详情	详情
(VI)	28715	3-chloro-N-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-1-propanamine		C₁₂H₁₆ClNO₂	详情	详情
(VII)	16186	(2R,3R)-2,3-bis(benzoyloxy)butanedioic acid		C₁₈H₁₄O₈	详情	详情
(VIII)	28716	3-chloro-N-[(2R)-2,3-dihydro-1,4-benzodioxin-2-ylmethyl]-1-propanamine		C₁₂H₁₆ClNO₂	详情	详情

Extended Information