4-cyano-2-fluorobenzoic acid -Drug Synthesis Database

【结构式】

【分子编号】28090

【品名】4-cyano-2-fluorobenzoic acid

【CA登记号】

【分子式】C₈H₄FNO₂

【分子量】165.1237032

【元素组成】C 58.19% H 2.44% F 11.51% N 8.48% O 19.38%

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 known amino tetralone (I) was coupled with 4-cyano-2-fluorobenzoic acid (II) in the presence of EDC to give amide (III). Subsequent conversion of the nitrile group of (III) into the required amidine was achieved by the following sequence consisting of addition of SH2, followed by S-methylation to produce the iminothioether (IV), displacement of the methylthio group of (IV) with ammonium acetate, and then protection of the resulting amidine with di-tert-butyl dicarbonate, yielding the Boc-protected amidine (V). Basic hydrolysis of the ethyl ester group of (V) generated the corresponding carboxylic acid (VI). Finally, the Boc protecting group of (VI) was cleaved by means of trifluoroacetic acid.

参考文献中间体

合成目标

【1】 Fisher, M.J.; Harms, C.S.; Giese, U.; et al.; Fused bicyclic Gly-Asp beta-turn mimics with potent affinity for GPIIb-IIIa. Exploration of the arginine isostere. Bioorg Med Chem Lett 2000, 10, 4, 385.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	34936	ethyl 2-(6-amino-1-oxo-1,2,3,4-tetrahydro-2-naphthalenyl)acetate	C₁₄H₁₇NO₃	详情	详情
(II)	28090	4-cyano-2-fluorobenzoic acid	C₈H₄FNO₂	详情	详情
(III)	34937	ethyl 2-[6-[(4-cyano-2-fluorobenzoyl)amino]-1-oxo-1,2,3,4-tetrahydro-2-naphthalenyl]acetate	C₂₂H₁₉FN₂O₄	详情	详情
(IV)	34938	ethyl 2-[6-([2-fluoro-4-[imino(methylsulfanyl)methyl]benzoyl]amino)-1-oxo-1,2,3,4-tetrahydro-2-naphthalenyl]acetate	C₂₃H₂₃FN₂O₄S	详情	详情
(V)	34939	ethyl 2-[6-([4-[[(tert-butoxycarbonyl)amino](imino)methyl]-2-fluorobenzoyl]amino)-1-oxo-1,2,3,4-tetrahydro-2-naphthalenyl]acetate	C₂₇H₃₀FN₃O₆	详情	详情
(VI)	34940	2-[6-([4-[[(tert-butoxycarbonyl)amino](imino)methyl]-2-fluorobenzoyl]amino)-1-oxo-1,2,3,4-tetrahydro-2-naphthalenyl]acetic acid	C₂₅H₂₆FN₃O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

Protection of beta-alanine derivative (I) with di-tert-butyl dicarbonate afforded the tert-butyl carbamate (II). This was condensed with ethyl piperidine-4-acetate (III) using O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyuronium hexafluorophosphate (HATU) and diisopropyl ethylamine to give amide (IV). Subsequent Boc deprotection of (IV) with trifluoroacetic acid provided amine (V), which was coupled with 2-fluoro-4-cyanobenzoic acid (VI) in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and 1-hydroxybenzotriazole yielding (VII). Treatment of the resulting cyanobenzamide (VII) with SH2 and Et3N produced the corresponding thioamide, which was S-alkylated with MeI to give (VIII). Finally, displacement of the methylthio group of (VIII) with thiazolidine (IX) furnished the corresponding amidine.

参考文献中间体

合成目标

【1】 Hayashi, Y.; Harada, T.; Katada, J.; et al.; GPIIb/IIIa integrin antagonists with the new conformational restriction unit, trisubstituted beta-amino acid derivatives, and substituted benzamidine structure. J Med Chem 1998, 41, 12, 2345.
【2】 Hayashi, Y.; Harada, T.; Tachiki, A.; Katada, J. (Nippon Steel Corp.); Fibrinogen receptor antagonists and medicinal preparations containing the same as the active ingredient. EP 0852225; JP 1998017550; WO 9749682 .

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)	28085	3-amino-2,2-dimethylpentanoic acid		C₇H₁₅NO₂	详情	详情
(II)	28086	3-[(tert-butoxycarbonyl)amino]-2,2-dimethylpentanoic acid		C₁₂H₂₃NO₄	详情	详情
(III)	28087	4-Piperidineacetic acid ethyl ester; ethyl 2-(4-piperidinyl)acetate		C₉H₁₇NO₂	详情	详情
(IV)	28088	ethyl 2-(1-[3-[(tert-butoxycarbonyl)amino]-2,2-dimethylpentanoyl]-4-piperidinyl)acetate		C₂₁H₃₈N₂O₅	详情	详情
(V)	28089	ethyl 2-[1-(3-amino-2,2-dimethylpentanoyl)-4-piperidinyl]acetate		C₁₆H₃₀N₂O₃	详情	详情
(VI)	28090	4-cyano-2-fluorobenzoic acid		C₈H₄FNO₂	详情	详情
(VII)	28091	ethyl 2-(1-[3-[(4-cyano-2-fluorobenzoyl)amino]-2,2-dimethylpentanoyl]-4-piperidinyl)acetate		C₂₄H₃₂FN₃O₄	详情	详情
(VIII)	28092	ethyl 2-[1-[3-([2-fluoro-4-[imino(methylsulfanyl)methyl]benzoyl]amino)-2,2-dimethylpentanoyl]-4-piperidinyl]acetate		C₂₅H₃₆FN₃O₄S	详情	详情
(IX)	28093	1,3-thiazolidine	504-78-9	C₃H₇NS	详情	详情

Extended Information