3-cyano-N-hydroxybenzenecarboximidoyl chloride -Drug Synthesis Database

【结构式】

【分子编号】23358

【品名】3-cyano-N-hydroxybenzenecarboximidoyl chloride

【CA登记号】

【分子式】C₈H₅ClN₂O

【分子量】180.59328

【元素组成】C 53.21% H 2.79% Cl 19.63% N 15.51% O 8.86%

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)

3-Cyanobenzaldehyde oxime (I) was treated with N-chlorosuccinimide to afford hydroxyiminoyl chloride (II). Subsequent cycloaddition of the intermediate nitrile oxide, generated in situ from (II) and Et3N, with methyl methoxyacrylate (III) produced isoxazole (IV). Then, basic hydrolysis of the ester group, followed by treatment with SOCl2 provided acid chloride (V). Aminobiphenyl (VIII) was obtained by Suzuki coupling of 4-bromoaniline (VI) with boronic acid (VII) using a palladium catalyst. Condensation of (VIII) with acid chloride (V) in the presence of Et3N then gave amide (IX). Alternatively, amide (IX) was obtained by AlMe3-catalyzed condensation of ester (IV) with amine (VIII). Treatment of nitrile (IX) with HCl in MeOH-CHCl3 generated the corresponding iminoester (X) with concomitant cleavage of the N-tert-butyl group. Finally, reaction of this iminoester with methanolic ammonium carbonate afforded the target amidine.

参考文献中间体

合成目标

【1】 Wexler, R.R.; Bostrom, L.L.; Pinto, D.J.; Wrong, P.C.; Pruitt, J.R.; Knabb, R.M.; Estrella, M.J.; Quan, M.L.; Isoxazolines and isoxazoles as factor Xa inhibitor. 216th ACS Natl Meet (Aug. 23-27, Boston) 1998, Abst MEDI 077.
【2】 Quan, M.L.; Pinto, D.J.P.; Fevig, J.M.; Pruitt, J.R. (DuPont Pharmaceuticals Co.); Oxygen or sulfur containing heteroaromatics as fac. WO 9828282 .
【3】 Pinto, D.J.P.; Pruitt, J.R.; Fevig, J.M.; Quan, M.L. (DuPont Pharmaceuticals Co.); Phenyl-isoxazoles as factor Xa inhibitors. US 6187797 .

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)	23357	3-[(hydroxyimino)methyl]benzonitrile		C₈H₆N₂O	详情	详情
(II)	23358	3-cyano-N-hydroxybenzenecarboximidoyl chloride		C₈H₅ClN₂O	详情	详情
(IV)	23360	methyl 3-(3-cyanophenyl)-4-isoxazolecarboxylate		C₁₂H₈N₂O₃	详情	详情
(V)	23361	3-(3-cyanophenyl)-4-isoxazolecarbonyl chloride		C₁₁H₅ClN₂O₂	详情	详情
(VII)	23363	4'-amino-N-(tert-butyl)[1,1'-biphenyl]-2-sulfonamide		C₁₆H₂₀N₂O₂S	详情	详情
(VIII)	23364	3-(3-cyanophenyl)-4-isoxazolecarbonyl chloride		C₁₁H₅ClN₂O₂	详情	详情
(IX)	23365	N-[2'-[(tert-butylamino)sulfonyl][1,1'-biphenyl]-4-yl]-3-(3-cyanophenyl)-4-isoxazolecarboxamide		C₂₇H₂₄N₄O₄S	详情	详情
(X)	23366	methyl 3-[4-([[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]amino]carbonyl)-3-isoxazolyl]benzenecarboximidoate		C₂₄H₂₀N₄O₅S	详情	详情
(XII)	22700	methyl (E)-3-methoxy-2-propenoate	34846-90-7	C₅H₈O₃	详情	详情
(XVI)	22531	4-Bromoaniline; 4-Bromophenylamine	106-40-1	C₆H₆BrN	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The cyclization of the chlorooxime (I) with formylacetic methyl ester (II) by means of diazomethane and TEA gives the 3-(3-cyanophenyl)isoxazole-4-carboxylic acid methyl ester (III), which is condensed with 4'-amino-N-tert-butylbiphenyl-2-sulfonamide (IV) by means of AlMe3 to yield the corresponding amide (V). The methanolysis of the cyano group of (V) with HCl and methanol affords the iminoester (VI), which is finally converted into the target amidine by reaction with ammonium carbonate.

参考文献中间体

合成目标

【1】 Bostrom, L.L.; Knabb, R.M.; Wong, P.C.; Pinto, D.J.; Estrella, M.J.; Wexler, R.R.; Pruitt, J.R.; Wright, M.R.; Isoxazolines and isoxazoles as factor Xa inhibitors. Bioorg Med Chem Lett 2000, 10, 8, 685.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	23358	3-cyano-N-hydroxybenzenecarboximidoyl chloride	C₈H₅ClN₂O	详情	详情
(II)	51426	methyl 3-oxopropanoate	C₄H₆O₃	详情	详情
(III)	23360	methyl 3-(3-cyanophenyl)-4-isoxazolecarboxylate	C₁₂H₈N₂O₃	详情	详情
(IV)	23363	4'-amino-N-(tert-butyl)[1,1'-biphenyl]-2-sulfonamide	C₁₆H₂₀N₂O₂S	详情	详情
(V)	23365	N-[2'-[(tert-butylamino)sulfonyl][1,1'-biphenyl]-4-yl]-3-(3-cyanophenyl)-4-isoxazolecarboxamide	C₂₇H₂₄N₄O₄S	详情	详情
(VI)	23366	methyl 3-[4-([[2'-(aminosulfonyl)[1,1'-biphenyl]-4-yl]amino]carbonyl)-3-isoxazolyl]benzenecarboximidoate	C₂₄H₂₀N₄O₅S	详情	详情

Extended Information