1-[(cyanoimino)(phenoxy)methoxy]benzene -Drug Synthesis Database

【结构式】

【分子编号】25868

【品名】1-[(cyanoimino)(phenoxy)methoxy]benzene

【CA登记号】107-37-9

【分子式】C₁₄H₁₀N₂O₂

【分子量】238.24568

【元素组成】C 70.58% H 4.23% N 11.76% O 13.43%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(II)

The reaction of (E)-6-(3-aminophenyl)-6-(3-pyridyl)-5-hexenoic acid methyl ester (I) with diphenyl N-cyanocarbinimidate (II) in isopropanol gives the N-cyanoisourea (III), which is condensed with tert-butylamine (IV) in refluxing isopropanol yielding the guanidine derivative (IV). Finally, hydrolysis of the ester group of (IV) with NaOH affords the target compound.

参考文献中间体

合成目标

【1】 Soyka, R.; et al.; Guanidine derivatives as combined thromboxane A2 receptor antagonists and synthase inhibitors. J Med Chem 1999, 42, 7, 1235.

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)	25867	methyl (E)-6-(3-aminophenyl)-6-(3-pyridinyl)-5-hexenoate		C₁₈H₂₀N₂O₂	详情	详情
(II)	25868	1-[(cyanoimino)(phenoxy)methoxy]benzene	107-37-9	C₁₄H₁₀N₂O₂	详情	详情
(III)	25869	methyl (E)-6-(3-[[(cyanoimino)(phenoxy)methyl]amino]phenyl)-6-(3-pyridinyl)-5-hexenoate		C₂₆H₂₄N₄O₃	详情	详情
(IV)	17895	2-Amino-2-methylpropane; tert-butylamine; 2-methyl-2-propanamine	75-64-9	C₄H₁₁N	详情	详情
(V)	25870	methyl (E)-6-(3-[[(tert-butylamino)(cyanoimino)methyl]amino]phenyl)-5-methyl-6-(3-pyridinyl)-5-hexenoate		C₂₅H₃₁N₅O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Condensation of amine (I) with diphenyl cyanocarbonimidate (II) affords isourea (III), which is then converted into cyanoguanidine (V) by coupling with diamine (IV) in CH2Cl2. The final step for the synthesis of the desired product is the reaction of the primary amine group of (V) with the active ester (VI) obtained by activation of calvatic acid (VII) with N-hydroxysuccinimide (N-HOSu) and N,N'-dicyclohexyl-carbodiimide (DCC) in THF.

参考文献中间体

合成目标

【1】 Hirschfeld, J.; et al.; Iodoaminopotentidine and related compounds: A new class of ligands with high affinity and selectivity for the histamine H2 receptor. J Med Chem 1992, 35, 12, 2231.
【2】 Sorba, G.; Dubini, F.; Brenciaglia, M.I.; Bertinaria, M.; Scaltrito, M.M.; Di Stilo, A.; Gasco, A.; Anti-Helicobacter pylori agents endowed with H2-antagonist properties. Bioorg Med Chem Lett 2001, 11, 3, 403.

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)	16105	3-[3-(piperidinomethyl)phenoxy]-1-propanamine; 3-[3-(piperidinomethyl)phenoxy]propylamine		C₁₅H₂₄N₂O	详情	详情
(II)	25868	1-[(cyanoimino)(phenoxy)methoxy]benzene	107-37-9	C₁₄H₁₀N₂O₂	详情	详情
(III)	48290	1-[3-(3-[[(cyanoimino)(phenoxy)methyl]amino]propoxy)benzyl]piperidine		C₂₃H₂₈N₄O₂	详情	详情
(IV)	22344	1,6-hexanediamine; 6-aminohexylamine	124-09-4	C₆H₁₆N₂	详情	详情
(V)	48291	N-(6-aminohexyl)-N''-cyano-N'-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]guanidine		C₂₃H₃₈N₆O	详情	详情
(VI)	48292	2-cyano-1-(4-[[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl]phenyl)-1-oxidodiazen-1-ium		C₁₂H₈N₄O₅	详情	详情
(VII)	48293	(E)-1-(4-carboxyphenyl)-2-cyano-1-oxidodiazen-1-ium		C₈H₅N₃O₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

The asymmetric epoxidation of (R)-2-methyl-6-nitro-2H-1-benzopyran-2-carbaldehyde (I) with NaOCl catalyzed by the chiral catalyst Mn(III)-Salen gives the chiral epoxide (II), which is opened by means of NH3 in hot ethanol to yield the amino alcohol (III). The reaction of (III) with diphenylcyanocarbonimidate (IV) by means of TEA in DMF/isopropanol affords the N-cyano-O-phenylisourea (V), which by reaction with benzylamine (VI) in the same solvent provides the N-cyanoguanidine (VII). Finally, the nitro group of this compound is reduced with H2 over Pd/C or NaBH4 in methanol to give the target amino derivative.

参考文献中间体

合成目标

【1】 Lee, S.; Yoo, S.; Yi, K.Y.; et al.; A novel anti-ischemic ATP-sensitive potassium channel (KATP) opener without vasorelaxation: N-(6-aminobenzopyranyl)-N-benzyl-N'-cyanoguanidine analogue. J Med Chem 2001, 44, 24, 4207.

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)	51836	(2S)-2-(dimethoxymethyl)-2-methyl-6-nitro-2H-chromene; methoxy[(2S)-2-methyl-6-nitro-2H-chromen-2-yl]methyl methyl ether		C₁₃H₁₅NO₅	详情	详情
(II)	57013	(1aS,2S,7bS)-2-(dimethoxymethyl)-2-methyl-6-nitro-1a,7b-dihydro-2H-oxireno[2,3-c]chromene; [(1aS,2S,7bS)-2-methyl-6-nitro-1a,7b-dihydro-2H-oxireno[2,3-c]chromen-2-yl](methoxy)methyl methyl ether		C₁₃H₁₅NO₆	详情	详情
(III)	51838	(2S,3S,4R)-4-amino-2-(dimethoxymethyl)-2-methyl-6-nitro-3,4-dihydro-2H-chromen-3-ol		C₁₃H₁₈N₂O₆	详情	详情
(IV)	25868	1-[(cyanoimino)(phenoxy)methoxy]benzene	107-37-9	C₁₄H₁₀N₂O₂	详情	详情
(V)	57014	(2S,3S,4R)-4-{[(cyanoimino)(phenoxy)methyl]amino}-2-(dimethoxymethyl)-3-hydroxy-2-methyl-6-nitro-3,4-dihydro-2H-chromene		C₂₁H₂₂N₄O₇	详情	详情
(VI)	15147	Benzylamine; Phenylmethanamine	100-46-9	C₇H₉N	详情	详情
(VII)	51841	N-benzyl-N''-cyano-N'-[(2S,3S,4R)-2-(dimethoxymethyl)-3-hydroxy-2-methyl-6-nitro-3,4-dihydro-2H-chromen-4-yl]guanidine		C₂₂H₂₅N₅O₆	详情	详情

Extended Information