2-nitro-3-pyridinol -Drug Synthesis Database

【结构式】

【分子编号】26207

【品名】2-nitro-3-pyridinol

【CA登记号】15128-82-2

【分子式】C₅H₄N₂O₃

【分子量】140.09844

【元素组成】C 42.87% H 2.88% N 20% O 34.26%

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：(IV)

Title radiolabeled compound has been obtained by several related procedures. Protection of (S)-2-azetidinecarboxylic acid (I) with tert-butyl dicarbonate provided carbamate (II), which was reduced to alcohol (III) using borane-dimethyl sulfide in THF at -78 C (1, 3). Subsequent coupling of (III) with 3-hydroxy-2-nitropyridine (IV) under Mitsunobu conditions gave ether (V). Introduction of the 18F in (IV) was performed by means of [18F]KF-Kryptofix K222 complex in DMSO, either by conventional heating at 150 C or by microwave activation yielding (VI). The resulting radiolabeled fluoropyridine (VI) was finally deprotected with trifluoroacetic acid in CH2Cl2.

参考文献中间体

合成目标

【1】 Dolle, F.; et al.; Synthesis of 2-[18F]fluoro-3-[2(s)-azetidnylmethoxy]pyridine, a higly potent radioligand for in vivo imaging central nicotinic acetylcholine receptors. J Label Compd Radiopharm 1998, 41, 451-463.

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)	26204	(2S)-2-azetidinecarboxylic acid; (S)-(-)-Azetidine carboxylic acid	2133-34-8	C₄H₇NO₂	详情	详情
(II)	26205	(2S)-1-(tert-butoxycarbonyl)-2-azetidinecarboxylic acid		C₉H₁₅NO₄	详情	详情
(III)	26206	tert-butyl (2S)-2-(hydroxymethyl)-1-azetidinecarboxylate		C₉H₁₇NO₃	详情	详情
(IV)	26207	2-nitro-3-pyridinol	15128-82-2	C₅H₄N₂O₃	详情	详情
(V)	26208	tert-butyl (2S)-2-[[(2-nitro-3-pyridinyl)oxy]methyl]-1-azetidinecarboxylate		C₁₄H₁₉N₃O₅	详情	详情
(VI)	26209	tert-butyl (2S)-2-[[(2-fluoro-3-pyridinyl)oxy]methyl]-1-azetidinecarboxylate		C₁₄H₁₉FN₂O₃	详情	详情
(VI)	26215	tert-butyl (2S)-2-[[(2-fluoro-3-pyridinyl)oxy]methyl]-1-azetidinecarboxylate		C₁₄H₁₉FN₂O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IX)

Mitsunobu coupling between 1(S)-(2,6-dichloro-3-fluorophenyl) ethanol (VIII) and 3-hydroxy-2-nitropyridine (IX) in the presence of DIAD and PPh3 affords ether (X), which by subsequent nitro group reduction using iron and HCl in EtOH yields the aminopyridine (XI). Bromination of compound (XI) by treatment with N-bromosuccinimide provides the bromopyridine (I), which is then submitted to palladium-catalyzed coupling with the pyrazolyl boronate (XII) to give adduct (VII). Finally, the N-Boc protecting group is removed by treatment with HCl .

参考文献中间体

合成目标

【1】 Tran-Dube, M., Shen, H., Yamazaki, S. et al. Lead optimization of 2-amino-3-benzyloxy-5-pyrazol-4-yl-pyridine for the discovery of clinical candidate PF-2341066 as potent and highly selective c-Met inhibitor. 235th ACS Natl Meet (April 6-10, New Orleans) 2008, Abst MEDI 105.

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)	68698	5-bromo-3-[1(R)-(2,6-dichloro-3-fluorophenyl)ethyl]-pyridin-2-amine;(R)-5-bromo-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-2-amine		C₁₃H₁₀BrCl₂FN₂O	详情	详情
(VII)	68693	(R)-tert-butyl 4-(4-(6-amino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate		C₂₆H₃₀Cl₂FN₅O₃	详情	详情
(VIII)	68699	1(S)-(2,6-dichloro-3-fluorophenyl)ethanol;(S)-1-(2,6-dichloro-3-fluorophenyl)ethanol	877397-65-4	C₈H₇Cl₂FO	详情	详情
(IX)	26207	2-nitro-3-pyridinol	15128-82-2	C₅H₄N₂O₃	详情	详情
(X)	68700	(R)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-2-nitropyridine		C₁₃H₉Cl₂FN₂O₃	详情	详情
(XI)	68701	(R)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-2-amine		C₁₃H₁₁Cl₂FN₂O	详情	详情
(XII)	68702	tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate		C₁₉H₃₂BN₃O₄	详情	详情

Extended Information