2-amino-2-(3-pyridinyl)acetonitrile -Drug Synthesis Database

【结构式】

【分子编号】16175

【品名】2-amino-2-(3-pyridinyl)acetonitrile

【CA登记号】

【分子式】C₇H₇N₃

【分子量】133.1528

【元素组成】C 63.14% H 5.3% N 31.56%

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：(II)

The reaction of pyridine-3-carbaldehyde (I) with KCN in acetic acid, followed by a treatment with NH4Cl in aqueous NH4OH yields 2-amino-2-(3-pyridyl)acetonitrile (II), which is cyclized to 3-chloro-4-(3-pyridyl)-1,2,5-thiadiazole (III) by a treatment with S2Cl2 in DMF. The reaction of (III) with sodium hexyloxide in hexanol yields 3-(hexyloxy)-4-(3-pyridyl)-1,2,5-thiadiazole (IV), which is treated with methyl iodide in acetone to afford the corresponding N-methylpyridinium salt (V). Finally, this compound is hydrogenated with NaBH4 in ethanol and salified with oxalic or L-tartaric acid in acetone or isopropanol.

参考文献中间体

合成目标

【1】 Graul, A.; Castaner, J.; Xanomeline. Drugs Fut 1996, 21, 9, 911.
【2】 Sauerberg, P.; Olesen, P.H. (Ferrosan A/S); Piperidine cpds. and their preparation and use. EP 0384288; US 5260311; US 5264444; US 5328925 .
【3】 Sauerberg, P.; Olesen, P.H.; Mitch, c.H. (Novo Nordisk A/S); Heterocyclic cpds. and their preparation and use. EP 0687265; JP 1996507298; WO 9420495 .
【4】 Osborne, L.M.; Shipley, L.A.; Treppendahl, S.; Petersen, T.G. (Novo Nordisk A/S); Heterocyclic chemistry. US 5834495; WO 9429303 .
【5】 Sauerberg, P.; Olesen, P.H.; Nielsen, S.; et al.; Novel functional M1selective muscarinic agonists. Synthesis and structure-activity relationships of 3-(1,2,5-thiadiazolyl)-1,2,5,6-tetrahydro-1-methylpyridines. J Med Chem 1992, 35, 12, 2274-83.

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)	12849	Nicotinaldehyde; 3-Pyridinecarboxaldehyde	500-22-1	C₆H₅NO	详情	详情
(II)	16175	2-amino-2-(3-pyridinyl)acetonitrile		C₇H₇N₃	详情	详情
(III)	16176	3-(4-chloro-1,2,5-thiadiazol-3-yl)pyridine		C₇H₄ClN₃S	详情	详情
(IV)	16177	3-[4-(hexyloxy)-1,2,5-thiadiazol-3-yl]pyridine; hexyl 4-(3-pyridinyl)-1,2,5-thiadiazol-3-yl ether		C₁₃H₁₇N₃OS	详情	详情
(V)	16178	3-[4-(hexyloxy)-1,2,5-thiadiazol-3-yl]-1-methylpyridinium iodide		C₁₄H₂₀IN₃OS	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The reaction of pyridine-3-carbaldehyde (I) with KCN in HOAc/water gives the cyanohydrine (II), which is treated with NH4Cl and NH3 in water to yield 2-amino-2-(3-pyridyl)acetonitrile (III). The cyclization of (III) with S2Cl2 in DMF affords 3-chloro-4-(3-pyridyl)-1,2,5-thiadiazole (IV), which is condensed with tetraethyleneglycol (V) by means of NaH in THF to provide the disubstituted tetraethyleneglycol (VI). The methylation of the pyridine rings of (VI) with methyl iodide in acetone gives the bis N-methylpyridinium derivative (VII), which is finally selectively reduced with NaBH4 in methanol and treated with HCl in the same solvent to furnish the target bis-tetrahydropyridine compound, isolated as the dihydrochloride salt.

参考文献中间体

合成目标

【1】 Rajeswaran, W.G.; Cao, Y.; Huang, X.-P.; et al.; Design, synthesis, and biological characterization of bivalent 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as selective muscarinic agonists. J Med Chem 2001, 44, 26, 4563.
【2】 Cao, Y.; Rajeswaran, W.G.; Messer, W.S. (University of Toledo); Muscarinic receptor agonists. US 6211204 .

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)	12849	Nicotinaldehyde; 3-Pyridinecarboxaldehyde	500-22-1	C₆H₅NO	详情	详情
(II)	53579	2-hydroxy-2-(3-pyridinyl)acetonitrile	n/a	C₇H₆N₂O	详情	详情
(III)	16175	2-amino-2-(3-pyridinyl)acetonitrile		C₇H₇N₃	详情	详情
(IV)	16176	3-(4-chloro-1,2,5-thiadiazol-3-yl)pyridine		C₇H₄ClN₃S	详情	详情
(V)	53580	Tetraethylene glycol; Tetraglycol	112-60-7	C₈H₁₈O₅	详情	详情
(VI)	53581	3-[4-(2-{2-[2-(2-{[4-(3-pyridinyl)-1,2,5-thiadiazol-3-yl]oxy}ethoxy)ethoxy]ethoxy}ethoxy)-1,2,5-thiadiazol-3-yl]pyridine; 4-(3-pyridinyl)-1,2,5-thiadiazol-3-yl 2-{2-[2-(2-{[4-(3-pyridinyl)-1,2,5-thiadiazol-3-yl]oxy}ethoxy)ethoxy]ethoxy}ethyl ether	n/a	C₂₂H₂₄N₆O₅S₂	详情	详情
(VII)	53582	1-methyl-3-[4-(2-{2-[2-(2-{[4-(1-methyl-3-pyridiniumyl)-1,2,5-thiadiazol-3-yl]oxy}ethoxy)ethoxy]ethoxy}ethoxy)-1,2,5-thiadiazol-3-yl]pyridinium diiodide	n/a	C₂₄H₃₀I₂N₆O₅S₂	详情	详情

Extended Information