1-(2-pyridinyl)piperazine -Drug Synthesis Database

【结构式】

【分子编号】24399

【品名】1-(2-pyridinyl)piperazine

【CA登记号】34803-66-2

【分子式】C₉H₁₃N₃

【分子量】163.22244

【元素组成】C 66.23% H 8.03% N 25.74%

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)

Pentafluorophenylalanine methyl ester (I) was treated with phosgene and pyridine to afford isocyanate (II), which was condensed with 5-aminothiadiazole-2-thione (III) to provide urea (IV). Then, displacement of the ester function of (IV) with 1-(2-pyridyl)piperazine (V) furnished the title amide.

参考文献中间体

合成目标

【1】 Mitchell, M.A.; Hendges, S.K.; Jacobsen, E.J.; et al.; Synthesis of a series of stromelysin-selective thiadiazole urea matrix metalloproteinase inhibitors. J Med Chem 1999, 42, 9, 1525.

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)	24395	methyl (2S)-2-amino-3-(2,3,4,5,6-pentafluorophenyl)propanoate		C₁₀H₈F₅NO₂	详情	详情
(II)	24396	methyl (2S)-2-isocyanato-3-(2,3,4,5,6-pentafluorophenyl)propanoate		C₁₁H₆F₅NO₃	详情	详情
(III)	24397	5-amino-1,3,4-thiadiazole-2(3H)-thione	2349-67-9	C₂H₃N₃S₂	详情	详情
(IV)	24398	methyl (2S)-3-(2,3,4,5,6-pentafluorophenyl)-2-([[(5-thioxo-4,5-dihydro-1,3,4-thiadiazol-2-yl)amino]carbonyl]amino)propanoate		C₁₃H₉F₅N₄O₃S₂	详情	详情
(V)	24399	1-(2-pyridinyl)piperazine	34803-66-2	C₉H₁₃N₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

(S)-Pipecolinic acid (I) was protected as the Fmoc-derivative (II) using 9-fluorenylmethyl chloroformate and Na2CO3. Subsequent coupling of (II) with O-(tert-butyldiphenylsilyl)hydroxylamine (III) by means of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) provided the silyl hydroxamate (IV). Removal of the Fmoc group of (IV) was then achieved by treatment with diethylamine in THF to provide (V). Treatment of N-(2-pyridyl)piperazine (VI) with chlorosulfonic acid and then with phosphorus pentachloride afforded the sulfamyl chloride (VII). This was coupled with piperidine (V) in the presence of Et3N to yield the sulfamide derivative (VIII). Finally, removal of the silyl protecting group of (VIII) was carried out with tetrabutylammonium fluoride in CH2Cl2.

参考文献中间体

合成目标

【1】 Mitchell, L.J. Jr.; Burke, B.; Dagostino, E.; et al.; Novel sulfamides and sulfonamide inhibitors of matrix metalloproteases. 218th ACS Natl Meet (Aug 22 1999, New Orleans) 1999, Abst MEDI 76.

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)	17380	(2S)hexahydro-2-pyridinecarboxylic acid; (S)-pipecolic acid	3105-95-1	C₆H₁₁NO₂	详情	详情
(II)	25357	(2S)-1-[(9H-fluoren-9-ylmethoxy)carbonyl]-2-piperidinecarboxylic acid		C₂₁H₂₁NO₄	详情	详情
(III)	33013	O-[tert-butyl(diphenyl)silyl]hydroxylamine; (aminooxy)(tert-butyl)diphenylsilane		C₁₆H₂₁NOSi	详情	详情
(IV)	33009	9H-fluoren-9-ylmethyl (2R)-2-[([[tert-butyl(diphenyl)silyl]oxy]amino)carbonyl]-1-piperidinecarboxylate		C₃₇H₄₀N₂O₄Si	详情	详情
(V)	33010	(2R)-N-[[tert-butyl(diphenyl)silyl]oxy]-2-piperidinecarboxamide		C₂₂H₃₀N₂O₂Si	详情	详情
(VI)	24399	1-(2-pyridinyl)piperazine	34803-66-2	C₉H₁₃N₃	详情	详情
(VII)	33011	4-(2-pyridinyl)-1-piperazinesulfonyl chloride		C₉H₁₂ClN₃O₂S	详情	详情
(VIII)	33012	(2R)-N-[[tert-butyl(diphenyl)silyl]oxy]-1-[[4-(2-pyridinyl)-1-piperazinyl]sulfonyl]-2-piperidinecarboxamide		C₃₁H₄₁N₅O₄SSi	详情	详情

Extended Information