3,5-dibromopyridine -Drug Synthesis Database

【结构式】

【分子编号】48045

【品名】3,5-dibromopyridine

【CA登记号】625-92-3

【分子式】C₅H₃Br₂N

【分子量】236.89356

【元素组成】C 25.35% H 1.28% Br 67.46% N 5.91%

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：(I)

Ispronicline can be synthesized as follows. The reaction of 3,5-dibromopyridine (I) with potassium isopropoxide (II) and powdered Cu in isopropanol at 140 °C gives 3-bromo-5-isopropoxypyridine (III), which is condensed with 4-penten-2(R)-ol (IV) by means of Pd(OAc)2, TOTP and TEA in acetonitrile at 140 °C to yield [2(R),4(E)]-5-(5-isopropoxypyridin-3-yl)-4-penten-2-ol (V). The treatment of (V) with Ts-Cl in pyridine affords the corresponding tosylate (VI), which is finally treated with methylamine in ethanol/water to obtain the target secondary amine (1-4). Scheme 1.

参考文献中间体

合成目标

【1】 Caldwell, W.S., Dull, G.M., Bhatti, B.S. et al. (R.J. Reynolds Tobacco Co.). Aryl substituted olefinic amines and their use as cholinergic receptor agonists. EP 1086082, JP 2002518373, WO 9965876.
【2】 Dull, M.D., Miller, C.H., Caldwell, W.S. et al. (Targacept, Inc.). Pharmaceutical compositions and methods for use. EP 1185514, JP 2003501416, US 6492399, WO 0075110.
【3】 Bencherif, M. (R.J. Reynolds Tobacco Co.). Pharmaceutical compositions for the prevention and treatment of central nervous system disorders. CA 2335012, EP 1102588, US 6218383, WO 0007600.
【4】 Caldwell, W.S., Dull, G.M., Bhatti, B.S. et al. (Targacept, Inc.). Compounds capable of activating cholinergic receptors. EP 1556352, JP 2006511482, US 2003125345, US 6979695, WO 2004031151.

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)	48045	3,5-dibromopyridine	625-92-3	C₅H₃Br₂N	详情	详情
(II)	65580	2-Propanol Potassium salt	6831-82-9	C₃H₇KO	详情	详情
(III)	65581	3-Bromo-5-isopropoxypyridine; 3-Bromo-5-[(1-methylethyl)oxy]pyridine; 3-Bromo-5-(1-methylethoxy)pyridine; 5-Bromo-3-isopropoxypyridine; 5-Isopropoxy-3-bromopyridine	212332-40-6	C₈H₁₀BrNO	详情	详情
(IV)	65582	(R )-(-)-4-Penten-2-ol	64584-92-5	C₅H₁₀O	详情	详情
(V)	65583	[(2R),(4E)]-5-(5-isopropoxypyridin-3-yl)-4-penten-2-ol		C₁₃H₁₉NO₂	详情	详情
(VI)	65584			C₂₀H₂₅NO₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Reaction of 3,5-dibromopyridine (I) with sodium ethoxide gave 3-bromo-5-ethoxypyridine (II). Palladium-catalyzed coupling of bromopyridine (II) with 3-buten-1-ol (III) yielded the pyridinylbutenol (IV), which was further converted to tosylate (V). Displacement of the tosylate group of (V) with methylamine then gave amine (VI).

参考文献中间体

合成目标

【1】 Caldwell, W.S.; Dull, G.M.; Miller, C.H.; [3-(5-Ethoxypyridin)yl]-alkenyl 1 amine cpds.. US 5616716 .
【2】 Dull, G.M.; Dobson, G.P.; Caldwell, W.S. (R.J. Reynolds Tobacco Co.); Pharmaceutical compsns. for prevention and treatment of central nervous system disorders. WO 9740011 .

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)	48045	3,5-dibromopyridine	625-92-3	C₅H₃Br₂N	详情	详情
(II)	48046	3-bromo-5-ethoxypyridine; 5-bromo-3-pyridinyl ethyl ether		C₇H₈BrNO	详情	详情
(III)	19743	3-buten-1-ol	627-27-0	C₄H₈O	详情	详情
(IV)	48047	(E)-4-(5-ethoxy-3-pyridinyl)-3-buten-1-ol		C₁₁H₁₅NO₂	详情	详情
(V)	48048	(E)-4-(5-ethoxy-3-pyridinyl)-3-butenyl 4-methylbenzenesulfonate		C₁₈H₂₁NO₄S	详情	详情
(VI)	48049	N-[(E)-4-(5-ethoxy-3-pyridinyl)-3-butenyl]-N-methylamine; (E)-4-(5-ethoxy-3-pyridinyl)-N-methyl-3-buten-1-amine		C₁₂H₁₈N₂O	详情	详情

Extended Information