超声刀品牌:阿尼西坦 [CAS:72432-10-1]合成路线图解??有机化学网

药物详细合成路线

Chemical Name： 1-p-Anisoyl-2-pyrrolidinone;1-(4-Methoxybenzoyl)pyrrolidin-2-one Generic Name： 阿尼西坦;Aniracetam Other Names： Aniracetam;Ro-13-5057;Reset;Ampamet;Sarpul;Draganon CAS： 72432-10-1 Formula： C₁₂H₁₃NO₃ Mole Weight： 219.24231 structure： Company： Roche (Originator), Biomedica Foscama (Licensee), Menarini (Licensee), Toyama (Licensee) Usage： Cognition Disorders, Treatment of, Mood Disorders, Treatment of, NEUROLOGIC DRUGS, PSYCHOPHARMACOLOGIC DRUGS, Senile Dementia, Treatment of Route 1 The silylation of 4-acetoxy-2-pyrrolidone (I) with trimethylchlorosilane (II) by means of triethyl amine in THF gives the corresponding N-trimethylsilyl derivative (III), which is condensed with 4-methoxybenzoyl chloride (IV) by means of NaHCO3 in THF yielding 1-(4-methoxybenzoyl)pyrrolin-2-one (V). Finally, this compound is reduced with H2 over Pd/C in ethyl acetate. Intermediates: Serial No. 4-ethyl-6-(trimethylsilyl)-1H-pyrano[3,4-c]pyridin-8-yl methyl ether; 4-ethyl-8-methoxy-6-(trimethylsilyl)-1H-pyrano[3,4-c]pyridine (IV) methyl (2E,4E)-6-[(2R,5S,7R,8S)-2-butyl-2-((1S)-1-[[tert-butyl(dimethyl)silyl]oxy]-2-propynyl)-8-methyl-1,6-dioxaspiro[4.5]dec-7-yl]-4-methyl-2,4-hexadienoate (I) (2E,4E)-6-[(2R,5S,7R,8S)-2-butyl-2-((1S)-1-[[tert-butyl(dimethyl)silyl]oxy]-2-propynyl)-8-methyl-1,6-dioxaspiro[4.5]dec-7-yl]-4-methyl-2,4-hexadienal (II) 1-[(4S)-4-isopropyl-2-thioxo-1,3-oxazolidin-3-yl]-1-propanone (III) (2R,3S,4E,6E)-8-[(2R,5S,7R,8S)-2-butyl-2-((1S)-1-[[tert-butyl(dimethyl)silyl]oxy]-2-propynyl)-8-methyl-1,6-dioxaspiro[4.5]dec-7-yl]-3-hydroxy-1-[(4S)-4-isopropyl-2-thioxo-1,3-oxazolidin-3-yl]-2,6-dimethyl-4,6-octadien-1-one (V) Reference 1:     Kyburz, E.; Aschwanden, W. (F. Hoffmann-La Roche AG); 1-(p-Methoxy-p-hydroxy, and p-benzyloxybenzoyl)-2-pyrrolidinones. DD 141828; EP 0005143; EP 0044088; ES 477587; ES 483756; JP 54117468 .
Route 2 The condensation of 4-aminobutyric acid (VI) with acid chloride (IV) by means of NaOH in water gives 4-(4-methoxybenzoylamino)butyric acid (VII), which is then cyclized by means of P2O5 in phosphoric acid. Intermediates: Serial No. 4,4-bipiperidine (VI) 4-ethyl-6-(trimethylsilyl)-1H-pyrano[3,4-c]pyridin-8-yl methyl ether; 4-ethyl-8-methoxy-6-(trimethylsilyl)-1H-pyrano[3,4-c]pyridine (IV) (2S,3S,4E,6E)-8-[(2R,5S,7R,8S)-2-butyl-2-((1S)-1-[[tert-butyl(dimethyl)silyl]oxy]-2-propynyl)-8-methyl-1,6-dioxaspiro[4.5]dec-7-yl]-2,6-dimethyl-4,6-octadiene-1,3-diol (VII) Reference 1:     Kyburz, E.; Aschwanden, W. (F. Hoffmann-La Roche AG); 1-(p-Methoxy-p-hydroxy, and p-benzyloxybenzoyl)-2-pyrrolidinones. DD 141828; EP 0005143; EP 0044088; ES 477587; ES 483756; JP 54117468 .
Route 3 By reaction of 2-pyrrolidinone (I) with p-methoxybenzoyl chloride (II) by means of triethylamine in ether or sodium hydride in DMF. Intermediates: Serial No. 4-ethyl-6-(trimethylsilyl)-1H-pyrano[3,4-c]pyridin-8-yl methyl ether; 4-ethyl-8-methoxy-6-(trimethylsilyl)-1H-pyrano[3,4-c]pyridine (II) benzhydryl (6R,7S)-3-[[(aminocarbonyl)oxy]methyl]-7-hydroxy-7-[[(Z)-1-methoxy-2-(2-thienyl)ethylidene]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate (I) Reference 1:     Kyburz, E.; Aschwanden, W.; 1-(P-Methoxy, p-hydroxy and p-benzyloxybenzoyl)-2-pyrrolidinones. EP 0005143; JP 54117468; US 4369139 . Reference 2:     Blancafort, P.; Serradell, M.N.; Mealy, N.E.; Leeson, P.A.; Castaner, J.; Aniracetam. Drugs Fut 1981, 6, 3, 127.