WAY-139799

Chemical Name: 3-Chloro-4-[2-(1,1-dimethylpropylamino)-3,4-dioxo-1-cyclobutenylaminomethyl]benzonitrile
CAS No. 202521-43-5
项目整合开发状态: Preclinical
项目研究机构: Wyeth Pharmaceuticals (Originator)
合成路线:A general synthetic route to a series of novel N-aryl and N-benzyl diaminocyclobutenedione derivatives and pertinent SAR data have been reported elsewhere.KCO-616 can be conveniently synthesized in two steps as shown in Scheme 26121401a.An ethanolic solution of 3,4-diethoxy-3-cyclobutene-1,2-dione (I) is allowed to react with tert-amylamine (II) at room temperature for a period of 24 h to give intermediate 3-(1,1-dimethylpropylamino)-4-ethoxy-3-cyclobutene-1,2-dione (III) in 90% isolated,purified yield.The condensation of this compound with 2,4-dichloro-6-methylbenzylamine (IV,recrystallized from boiling diethyl ether) in ethanol at room temperature for 24 h affords analytically pure 3-(2,4-dichloro-6-methylbenzylamino)-4-(1,1-dimethylpropylamino)-3-cyclobutene-1,2-dione (KCO-616) in 92% yield.

合成路线:Benzylic bromination of 3-chloro-4-methylbenzonitrile (I) by means of N-bromosuccinimide and azobis(isobutyronitrile) provided bromide (II).Subsequent displacement of the bromine atom of (III) by potassium phthalimide (III) afforded the N-substituted phthalimide (IV),which was then deprotected with ethanolic hydrazine to furnish the primary amine (V).

合成路线:Treatment of 3,4-dibutoxy-3-cyclobutene-1,2-dione (VI) with tert-butylamine (VII) yielded the amino cyclobutenedione (VIII).Subsequent condensation of (VIII) with 3-chloro-4-(aminomethyl)benzonitrile (V) in THF provided the target diamino derivative.

合成路线:Benzylic bromination of 3-chloro-4-methylbenzonitrile (I) by means of N-bromosuccinimide and azobis(isobutyronitrile) provided bromide (II).Subsequent displacement of the bromine atom of (II) by potassium phthalimide (III) afforded the N-substituted phthalimide (IV),which was then deprotected with ethanolic hydrazine to furnish the primary amine (V).

合成路线:Treatment of 3,4-dibutoxy-3-cyclobutene-1,2-dione (VI) with 1,1-dimethylpropylamine (VII) yielded the amino cyclobutenedione (VIII).Subsequent condensation of (VIII) with 3-chloro-4-(aminomethyl)benzonitrile (V) in THF provided the target diamino derivative.