合成路线1

The reaction of 5-amino-4-cyanooxazole (I) with tetramethyl orthocarbonate (II) in refluxing acetic anhydride gives 4-cyano-5-(diethoxymethyleneamino)oxazole (III), which is cyclized with propylamine (A) in refluxing ethanol yielding 5-methoxy-6-propyl-7(6H)-iminooxazolo[5,4-d]pyrimidine (IV), which is finally hydrolyzed and rearranged by treatment with NaOH in water at 100 C or with formamide at 180 C.

合成路线2

The condensation of epichlorohydrin (I) with 7-hydroxyflavone (II) by means of NaOH in ethanol - water gives 7-(2,3-epoxypropoxy)fIavone (III), which is then treated with propylamine (IV) in methanol, and neutralized with maleic acid.

合成路线3

The condensation of (3-methoxyphenyl)acetonitrile (VIII) with 3-bromopropyltetrahydropyranyl ether (IX) by means of lithium diisopropylamide in THF gives 2-(3-methoxyphenyl)-5-tetrahydropyranyloxypentanonitrile (X), which is oxidized with chromic anhydride-H2SO4 yielding 4-cyano-3-(3-methoxyphenyl)butyric acid (XI). The hydrolysis of (XI) with KOH in ethanol-water affords 2-(3-methoxyphenyl)glutaric acid (XII), which is anhydrized with refluxing acetic anhydride giving 2-(3-methoxyphenyl)glutaric anhydride (XIII). The reaction of (XIII) with propylamine (C) in refluxing benzene yields 2-(3-methoxyphenyl)-N-propylglutarimide (XIV), which is demethylated with BBr3 in methylene chloride to 2-(3-hydroxyphenyl)-N-propylglutarimide (XV). The benzylation of (XV) with benzyl bromide and K2CO3 in DMF affords 2-(3-benzyloxyphenyl)-N-propylglutarimide (XVI), which is reduced with LiAlH4 in THF giving 3-(3-benzyloxyphenyl)-N-propylpiperidine (XVII). Finally, this compound is debenzylated by hydrogenolysis with H2 over Pd/C in AcOH.

合成路线4

The cyclization of 4-benzoyloxycyclohexanone (I) with ethyl 2-bromomethylacrylate (II) and propylamine (III) in refluxing toluene gives ethyl 1-propyl-6-benzoyloxy-1,2,3,4,5,6,7,8-octahydroquinoline-3-carboxylate (IV), which is reduced with sodium cyanoborohydride in methanol yielding the corresponding decahydro derivative (V). Debenzoylation of (V) with NaOH in methanol affords the hydroxyquinoline (VI), which is oxidized with CrO3-pyr giving ethyl 1-propyl-6-oxodecahydroquinoline-3-carboxylate (VII). The reaction of (VII) with dimethylformamide dimethylacetal (VIII) in refluxing toluene yields ethyl 1-propyl-6-oxo-7-(dimethylaminomethylene)decahydroquinoline-3-carboxylate (IX), which is cyclized with hydrazine in ethanol affording ethyl 5-propyl-4,4a,5,6,7,8,8a,9-octahydro-2H-pyrazolo[3,4-g]quinoline-7-carboxylic acid (X). The reduction of (X) with LiAlH4 in THF gives the corresponding hydroxymethyl derivative (XI), which is esterified with methanesulfonyl chloride to the mesyl ester (XII). Finally, this compound is treated with methyl mercaptane and NaH in DMF.

合成路线5

8-OH-DPAT is conveniently prepared from 8-methoxy-2-tetralone (I) (1-3). Reductive amination of (I) gives 8-methoxy-2-(n-propylamino)tetralin (II). Subsequent N-acylation using propionyl chloride followed by LiAlH4 reduction yields 8-methoxy-2-(di-n-propylamino)tetralin (III). The title compound is obtained as the hydrobromide after O-demethylation of (III) in aqueous HBr.

合成路线6

The condensation of beta-phenyl-2-hydroxypropiophenone sodium salt (I) with 1-chloro-2,3-epoxypropane (A) at 100 C yields beta-phenyl-2-(2',3'-epoxypropoxy)propiophenone (II). which is then treated with n-propylamine (B) also at 100 C.

合成路线7

The reaction of propylamine (I) with di(2-pyridyl)thione (DPT) gives the corresponding isothiocyanate (II), which is condensed with cyanamide (III) and 2-bromo-1-(3-pyridyl)ethanone (IV) by means of NaOMe to yield the adduct (V). This compound, without isolation, cyclizes to the target thiazole.

合成路线8