4-Bromo-2,6-difluorophenol -Drug Synthesis Database

【结构式】

【分子编号】55556

【品名】4-Bromo-2,6-difluorophenol

【CA登记号】104197-13-9

【分子式】C₆H₃BrF₂O

【分子量】208.9900264

【元素组成】C 34.48% H 1.45% Br 38.23% F 18.18% O 7.66%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(VIII)

The reaction of malononitrile (I) with benzyl alcohol (II) and HCl in ethyl ether gives 2-cyanoacetimidic acid benzyl ester (III), which is condensed with phenoxycarbonyl isothiocyanate (IV) to yield 2-cyano-3-mercapto-3-(phenoxycarbonylamino)acrylimidic acid benzyl ester (V). Compound (V) is cyclized by means of pyridine and Br2 in acetonitrile to afford the isothiazole derivative (VI). The reaction of (VI) with conc. H2SO4 provides the isothiazole carboxamide (VII), which is condensed with 4-bromo-2,6-difluorophenol (VIII) by means of PPh3 and DEAD in THF to give the aromatic ether (IX). Finally, the carbamic ester group of (IX) is treated with 4-(1-pyrrolidinyl)butylamine (X) to yield the target urea derivative.

参考文献中间体

合成目标

【1】 Larson, E.R.; Noe, M.C.; Gant, T.G. (Pfizer Inc.); Isothiazole derivs. useful as anticancer agents. EP 1084114; JP 2002517384; US 6235764; WO 9962890 .

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)	12061	Malononitrile	109-77-3	C₃H₂N₂	详情	详情
(II)	18710	Benzyl alcohol; Phenylmethanol	100-51-6	C₇H₈O	详情	详情
(III)	55551	benzyl 2-cyanoethanimidoate		C₁₀H₁₀N₂O	详情	详情
(IV)	55552	1-[(isothiocyanatocarbonyl)oxy]benzene		C₈H₅NO₂S	详情	详情
(V)	55553	benzyl (Z)-2-cyano-3-[(phenoxycarbonyl)amino]-3-sulfanyl-2-propenimidoate		C₁₈H₁₅N₃O₃S	详情	详情
(VI)	55554	phenyl 3-(benzyloxy)-4-cyano-5-isothiazolylcarbamate		C₁₈H₁₃N₃O₃S	详情	详情
(VII)	55555	phenyl 4-(aminocarbonyl)-3-hydroxy-5-isothiazolylcarbamate		C₁₁H₉N₃O₄S	详情	详情
(VIII)	55556	4-Bromo-2,6-difluorophenol	104197-13-9	C₆H₃BrF₂O	详情	详情
(IX)	55557	phenyl 4-(aminocarbonyl)-3-(4-bromo-2,6-difluorophenoxy)-5-isothiazolylcarbamate		C₁₇H₁₀BrF₂N₃O₄S	详情	详情
(X)	55558	4-Pyrrolidinobutylamine		C₈H₁₈N₂	详情	详情

Extended Information