TC-2557(sesquifumarate), TC-2559, -Drug Synthesis Database

【结构式】

【药物名称】TC-2557(sesquifumarate), TC-2559

【化学名称】4-(5-Ethoxypyridin-3-yl)-N-methyl-3(E)-buten-1-amine D-galactarate (2:1)

【CA登记号】326924-19-0, 189274-78-0 (free base), 212332-35-9 (sesquifumarate)

【分子式】C₃₀H₄₆N₄O₁₀

【分子量】622.72192

【开发单位】Targacept (Originator)

【药理作用】Cognition Disorders, Treatment of, NEUROLOGIC DRUGS, Nicotinic Receptor Agonists

合成路线1 合成路线2

合成路线1

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

【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

合成路线2

In a related method, 4-bromo-1-butene (VII) was reacted with methylamine to produce the secondary amine (VIII). After protection of (VIII) as the tert-butyl carbamate (IX), palladium-catalyzed coupling with 3-bromo-5-ethoxypyridine (II) furnished adduct (X). The N-Boc protecting group of (X) was then cleaved under acidic conditions to afford amine precursor (VI). The title hemigalactarate salt was finally prepared by treatment of amine (VI) with D-galactaric acid in aqueous ethanol.

参考文献中间体

【1】 Bane, A.J.; Dull, G.M.; Bencherif, M.; Miller, C.H.; Gatto, G.J.; TC-2559: A novel orally active ligand selective at neuronal acetylcholine receptors. Eur J Pharmacol 2000, 409, 1, 45.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	48046	3-bromo-5-ethoxypyridine; 5-bromo-3-pyridinyl ethyl ether		C₇H₈BrNO	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
(VII)	11720	4-Bromo-1-butene	5162-44-7	C₄H₇Br	详情	详情
(VIII)	48050	N-(3-butenyl)-N-methylamine; N-methyl-3-buten-1-amine		C₅H₁₁N	详情	详情
(IX)	48051	tert-butyl 3-butenyl(methyl)carbamate		C₁₀H₁₉NO₂	详情	详情
(X)	48052	tert-butyl (E)-4-(5-ethoxy-3-pyridinyl)-3-butenyl(methyl)carbamate		C₁₇H₂₆N₂O₃	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)