1-chloro-4-methoxy-2-nitrobenzene -Drug Synthesis Database

【结构式】

【分子编号】24772

【品名】1-chloro-4-methoxy-2-nitrobenzene

【CA登记号】10298-80-3

【分子式】C₇H₆ClNO₃

【分子量】187.58228

【元素组成】C 44.82% H 3.22% Cl 18.9% N 7.47% O 25.59%

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)

A preparative-scale synthetic route for T-614 has been reported: The reaction of 4-chloro-3-nitroanisole (I) with potassium phenolate in hot DMF gives 4-phenoxy-3-nitroanisole (II), which is reduced to the corresponding 3-amino compound (III) by treatment with Fe and HCl. The reaction of (III) with mesyl chloride in pyridine affords the sulfonamide (IV), which is acylated with 2-aminoacetonitrile (V) and AlCl3 in nitrobenzene/HCl giving the 2-aminoacetophenone (VI). Formylation of (VI) at the NH2 with acetic formic anhydride yields the formamide (VII), which is demethylated with AlCl3 and NaI in acetonitrile affording the phenol (VIII). Finally, this compound is cyclized with dimethylformamide dimethylacetal in DMF.

参考文献中间体

合成目标

【1】 Yoshida, C.; Tanaka, K.; Nagaki, H.; Takeno, R.; Inaba, T.; Takano, S.; Synthesis and antiinflammatory activities of 7-methanesulfonylamino-6-phenoxychromones. Antiarthritic effect of the 3-formylamino compound (T-614) in chronic inflammatory disease models. Chem Pharm Bull 2000, 48, 1, 131.

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)	24772	1-chloro-4-methoxy-2-nitrobenzene	10298-80-3	C₇H₆ClNO₃	详情	详情
(II)	39674	4-methoxy-2-nitrophenyl phenyl ether; 4-methoxy-2-nitro-1-phenoxybenzene		C₁₃H₁₁NO₄	详情	详情
(III)	39675	5-methoxy-2-phenoxyphenylamine; 5-methoxy-2-phenoxyaniline		C₁₃H₁₃NO₂	详情	详情
(IV)	39676	N-(5-methoxy-2-phenoxyphenyl)methanesulfonamide		C₁₄H₁₅NO₄S	详情	详情
(V)	39680	2-aminoacetonitrile		C₂H₄N₂	详情	详情
(VI)	39677	N-[4-(2-aminoacetyl)-5-methoxy-2-phenoxyphenyl]methanesulfonamide		C₁₆H₁₈N₂O₅S	详情	详情
(VII)	39678	N-[4-[2-(formylamino)acetyl]-5-methoxy-2-phenoxyphenyl]methanesulfonamide		C₁₇H₁₈N₂O₆S	详情	详情
(VIII)	39679	N-[4-[2-(formylamino)acetyl]-5-hydroxy-2-phenoxyphenyl]methanesulfonamide		C₁₆H₁₆N₂O₆S	详情	详情
(IX)	11984	N-(Dimethoxymethyl)-N,N-dimethylamine;dimethylformamide dimethylacetal;1,1-dimethoxy-N,N-dimethylmethanamine； Dimethoxy-N,N-dimethylmethanamine; N,N-Dimethylformamide dimethyl acetal	4637-24-5	C₅H₁₃NO₂	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 reaction of 2-chloro-5-methoxynitrobenzene (I) with aniline (II) in basic medium gives the diphenylamine (III), which is reduced at the NO2 group with H2 over Pd/C in methanol yielding the o-phenylenediamine (IV). Finally, this compoud is cyclized with formamidine (V) in refluxing 2-methoxyethanol.

参考文献中间体

合成目标

【1】 Palmer, B.D.; Smaill, J.B.; Boyd, M.; Boschelli, D.H.; Doherty, A.M.; Hamby, J.M.; Khatana, S.S.; Kramer, J.B.; Kraker, A.J.; Panek, R.L.; Lu, G.H.; Dahring, T.K.; Winters, R.T.; Showalter, H.D.; Denny, W.A.; Structure-activity relationships for 1-phenylbenzimidazoles as selective ATP site inhibitors of the platelet-derived growth factor receptor. J Med Chem 1998, 41, 27, 5457.

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)	24772	1-chloro-4-methoxy-2-nitrobenzene	10298-80-3	C₇H₆ClNO₃	详情	详情
(II)	12294	Aniline; Phenylamine	62-53-3	C₆H₇N	详情	详情
(III)	24774	4-methoxy-2-nitro-N-phenylaniline		C₁₃H₁₂N₂O₃	详情	详情
(IV)	24775	4-methoxy-N(1)-phenyl-1,2-benzenediamine		C₁₃H₁₄N₂O	详情	详情
(V)	15369	Iminoformamide; Methanimidamide	463-52-5	CH₄N₂	详情	详情

Extended Information