【药物名称】AS-601811
化学结构式(Chemical Structure):
参考文献No.34042
标题:Benzo[c]quinolizine derivs., their preparation and use as 5alpha-reductases inhibitors
作者:Guarna, A.; Serio, M. (Applied Research Systems ARS Holdings NV)
来源:EP 0880520; JP 2000504680; WO 9729107
合成路线图解说明:

Acylation of p-toluidine (I) with 3-chloropropionyl chloride afforded the beta-chloroamide (II), which was cyclized to dihydroquinolinone (III) by treatment with AlCl3 at 120 C. After protection of the N atom of (III) as the tert-butyl carbamate (IV), reduction of the 2-oxo group by NaBH4 in ethanol at -25 C, followed by acidic quench with ethanolic HCl, afforded the N-Boc-2-ethoxy derivative (V). The tandem Mannich-Michael cyclization of the alpha-ethoxycarbamate (V) with the (silyloxy)diene (VII) (derived from 1-penten-3-one (VI) in the presence of trimethylsilyl triflate) furnished the benzoquinolizinone (VIII) as a mixture of diastereoisomers. Finally, oxidation of this mixture with mercuric acetate afforded the desired delta-4 unsaturated compound.

参考文献No.595087
标题:Benzo[c]quinolizin-3-ones: A novel class of potent and selective nonsteroidal inhibitors of human steroid 5alpha-reductase 1
作者:Guarna, A.; Machetti, F.; Occhiato, E.G.; Scarpi, D.; Comerci, A.; Danza, G.; Mancina, R.; Serio, M.; Hardy, K.
来源:J Med Chem 2000,43(20),3718
合成路线图解说明:

Acylation of p-toluidine (I) with 3-chloropropionyl chloride afforded the beta-chloroamide (II), which was cyclized to dihydroquinolinone (III) by treatment with AlCl3 at 120 C. After protection of the N atom of (III) as the tert-butyl carbamate (IV), reduction of the 2-oxo group by NaBH4 in ethanol at -25 C, followed by acidic quench with ethanolic HCl, afforded the N-Boc-2-ethoxy derivative (V). The tandem Mannich-Michael cyclization of the alpha-ethoxycarbamate (V) with the (silyloxy)diene (VII) (derived from 1-penten-3-one (VI) in the presence of trimethylsilyl triflate) furnished the benzoquinolizinone (VIII) as a mixture of diastereoisomers. Finally, oxidation of this mixture with mercuric acetate afforded the desired delta-4 unsaturated compound.

参考文献No.603226
标题:Modification of the aza-robinson annulation for the synthesis of 4-methyl-benzol[c]quinoliin-3-ones. Potent inhibitors of steroid 5alpha-reductase 1
作者:Guarna, A.; Lombardi, E.; Machetti, F.; Occhiato, E.G.; Scarpi, D.
来源:J Org Chem 2000,65(23),8093
合成路线图解说明:

The reaction of 6-methyl-1,2,3,4-tetrahydroquinolin-2-one (I) with Lawesson's reagent in refluxing toluene gives 6-methyl-1,2,3,4-tetrahydroquinolin-2-thione (II), which is condensed with ethyl vinyl ketone (III) by means of K2CO3 or DBU in THF to yield the addition product (IV). The reaction of (IV) with dimethyl sulfate in refluxing toluene affords the thioiminium ion (V), which, without isolation, is cyclized to the target compound by reaction with DBU in refluxing toluene.

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