GW-5074

3-(3,5-二溴-4-羟基苯亚甲基)-5-碘-1,3-二氢吲哚-2-酮Chemical Name: 3-(3,5-Dibromo-4-hydroxybenzylidene)-5-iodo-2,3-dihydro-1H-indol-2-one
CAS No. 220904-83-6
项目整合开发状态: Biological Testing
项目研究机构: GlaxoSmithKline (Originator)
合成路线:The key step is the aldol condensation between 5-iodooxiindole (I) and 3,5-dibromo-4-hydroxybenzaldehyde (II) in presence of HCl in HOAc.Alternatively catalytic acid conditions may be used such as p-toluenesulfonic acid in toluene at high temperature.

合成路线:5-Iodooxiindole (I) may be prepared by published procedures:1) Treatment of p-iodoaniline (IV) with the Sandmeyer isonitrosoacetanilide Isatin synthesis,by condensation with chloral hydrate (A) and hydroxylamine followed by cyclization with concentrated sulfuric acid and hydrolysis with water yields isatin (V).The conversion of (V) to (I) may be conducted via the Wolf-Kishner reduction by treatment with hydrazine hydrate in ethanol at 20-80 C to give hydrazide (VI).The conversion from (VI) to (I) may be performed by treatment with sodium ethoxide in a suitable solvent such as ethanol at 0-80 C.2) Iodoindole (VII) may be converted to the bromo derivative (VIII) by tretment with pyridinium perbromide in tert-butyl alcohol.The last step of the synthesis is the treatment of (VIII) with H2 over Pd/C in anhydrous ethanol,or by treatment with a solution of NH4Cl followed by treatment with activated zinc in THF.3) Iodoaniline (IV) can be converted to the sulfanylderivative (IX) by treatment with tert-butyl hypochlorite,followed by treatment with ethyl methylthioacetate (B) and triethylamine in dichloromethane.Finally the conversion of (IX) to the desired product may be conducted by means of W-2 Raney-Ni in EtOH or by treatment with activated zinc in THF.

合成路线:Also 3,5-dibromo-4-hydroxybenzaldehyde (II) is commercially available but it may also be prepared by published procedures:1) The synthesis can be performed by treating 2,6-dibromophenol (X) with hexamethylenetetramine in acetic acid.2) Alternatively the synthetic pathway can be the oxidation of 3,5-dibromo-4-hydroxytoluene (XI) by means of DDQ in dioxane with a small amount of water.