(2S)-2-azetidinecarboxylic acid; (S)-(-)-Azetidine carboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】26204

【品名】(2S)-2-azetidinecarboxylic acid; (S)-(-)-Azetidine carboxylic acid

【CA登记号】2133-34-8

【分子式】C₄H₇NO₂

【分子量】101.10512

【元素组成】C 47.52% H 6.98% N 13.85% O 31.65%

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)

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)

Condensation of 3,5-dichlorobenzenesulfonyl chloride (VIII) with (S)-azetidine-2-carboxylic acid (IX) under Schotten-Baumann conditions gives sulfonamide (X). This is subsequently coupled with aminoester (VII) by means of PyBOP to afford amide (XI). The methyl ester group of (XI) is finally hydrolyzed to the target carboxylic acid employing LiOH.

参考文献中间体

合成目标

【1】 Kopka, I.E.; Mumford, R.A.; Lin, L.S.; et al.; The discovery of acylated beta-amino acids as potent and orally bioavailable VLA-4 antagonists. Bioorg Med Chem Lett 2002, 12, 4, 611.
【2】 Hagmann, W.K.; Durette, P.L.; Mumford, R.A.; Kopka, I.E.; Mills, S.G.; MacCoss, M.; Magriotis, P.A. (Merck & Co., Inc.); Substd. beta-alanine derivs. as cell adhesion inhibitors. WO 0071572 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIII)	59023	3,5-dichlorobenzenesulfonyl chloride		C₆H₃Cl₃O₂S	详情	详情
(IX)	26204	(2S)-2-azetidinecarboxylic acid; (S)-(-)-Azetidine carboxylic acid	2133-34-8	C₄H₇NO₂	详情	详情
(X)	59024	(2S)-1-[(3,5-dichlorophenyl)sulfonyl]-2-azetidinecarboxylic acid		C₁₀H₉Cl₂NO₄S	详情	详情
(XI)	59022	methyl (3R)-3-amino-3-(4-methoxyphenyl)propanoate		C₁₁H₁₅NO₃	详情	详情
(XII)	59025	methyl (3R)-3-[({(2S)-1-[(3,5-dichlorophenyl)sulfonyl]azetidinyl}carbonyl)amino]-3-(4-methoxyphenyl)propanoate		C₂₁H₂₂Cl₂N₂O₆S	详情	详情

Extended Information