【药物名称】S-31411(racemate), S-32504
化学结构式(Chemical Structure):
参考文献No.38670
标题:Disubstd. trans-3,4,4a,5,6,10b-hexahydro-2H-napht(1,2-b)-1,4-oxazines, process for their preparation and pharmaceutical compsns. containing them
作者:Millan, M.; Lejeune, F.; Peglion, J.-L.; Harmange, J.-C. (ADIR et Cie.)
来源:CA 2246482; EP 0899267; FR 2767825; JP 1999130759; US 6025356
合成路线图解说明:

Nitrosation of 7-methoxy-2-tetralone (I) using isoamyl nitrite and potassium tert-butoxide provided the oximino ketone (II). Catalytic hydrogenation of the oxime function of (II) in the presence of propionic anhydride gave rise to the propionamide (III). Ketone reduction by means of NaBH4 produced a mixture of cis- and trans-hydroxy amides from which the pure trans-isomer (IV) was isolated after two recrystallizations from EtOAc. The amide function of (IV) was subsequently reduced with LiAlH-4 to the N-propyl amine (V). Acylation of amino alcohol (V) with chloroacetyl chloride (VI) afforded the corresponding chloroacetamido alcohol (VII), which was further cyclized to compound (VIII) upon treatment with NaH. The lactam carbonyl group of (VIII) was then reduced with borane-dimethyl sulfide complex to the cyclic amine (IX). Methyl ether cleavage in (IX) to produce phenol (X) was then achieved by heating with pyridine hydrochloride (1). Phenol (X) was converted to the aryl triflate (XI) by treatment with trifluoromethanesulfonic anhydride. Displacement of the triflate group of (XI) with zinc cyanide in the presence of Pd catalyst furnished nitrile (XII). Partial hydrolysis of the nitrile (XII) under basic conditions produced the corresponding racemic amide. The title dextro-enantiomer was then isolated by preparative chiral HPLC.

参考文献No.629834
标题:Discovery of S32504. A preferential agonist at dopamine D3 vs. D2 receptors possessing antiparkinsonian and antidepressant properties
作者:Peglion, J.-L.; et al.
来源:222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001,Abst MEDI 208
合成路线图解说明:

Nitrosation of 7-methoxy-2-tetralone (I) using isoamyl nitrite and potassium tert-butoxide provided the oximino ketone (II). Catalytic hydrogenation of the oxime function of (II) in the presence of propionic anhydride gave rise to the propionamide (III). Ketone reduction by means of NaBH4 produced a mixture of cis- and trans-hydroxy amides from which the pure trans-isomer (IV) was isolated after two recrystallizations from EtOAc. The amide function of (IV) was subsequently reduced with LiAlH-4 to the N-propyl amine (V). Acylation of amino alcohol (V) with chloroacetyl chloride (VI) afforded the corresponding chloroacetamido alcohol (VII), which was further cyclized to compound (VIII) upon treatment with NaH. The lactam carbonyl group of (VIII) was then reduced with borane-dimethyl sulfide complex to the cyclic amine (IX). Methyl ether cleavage in (IX) to produce phenol (X) was then achieved by heating with pyridine hydrochloride (1). Phenol (X) was converted to the aryl triflate (XI) by treatment with trifluoromethanesulfonic anhydride. Displacement of the triflate group of (XI) with zinc cyanide in the presence of Pd catalyst furnished nitrile (XII). Partial hydrolysis of the nitrile (XII) under basic conditions produced the corresponding racemic amide. The title dextro-enantiomer was then isolated by preparative chiral HPLC.

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