Patent ID: 6100399
Filing Date: 2000-08-08
Classification: C07D

Abstract:
A process of making a compound of Formula (I) ##STR27## wherein R is hydrogen, an unsubstituted or substituted C.sub.1-10 alkyl, unsubstituted or substituted aryl, halogen, hydroxyl, thiol, C.sub.1-10 alkoxy, C.sub.1-10 alkylthio, C.sub.1-10 alkylsulfinyl, CH.sub.2 OR.sub.12, amino, mono or di-C.sub.1-10 alkyl substituted amino, NHR.sub.21, N(R.sub.10)C(O)R.sub.a or an N-heterocyclyl ring which ring has from 5 to 7 members and does or does not contain an additional heteroatom selected from oxygen, sulfur or NR.sub.15 ;Z.sub.1 is N(R.sup.d).sub.2, SR.sup.e, OR.sup.e, or R.sup.d ;R.sup.d is independently hydrogen, alkyl, aryl, heteroaryl, cycloalkyl, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclic, or heterocyclicalkyl, all of which are unsubstituted or substituted;R.sup.e is alkyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, arylalkyl, heteroarylalkyl, heterocyclic, or heterocyclicalkyl, all of which are unsubstituted or substituted;R.sub.4 is an unsubstituted or substituted phenyl, naphth-1-yl or naphth-2-yl, or heteroaryl ring;m is 0, or the integer 1 or 2;m' is an integer having a value of 1 or 2,R.sub.a is hydrogen, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, aryl, arylC.sub.1-4 alkyl, heteroaryl, heteroarylC.sub.1-4 alkyl, heterocyclyl, or heterocyclylC.sub.1-4 alkyl;R.sub.2 is --(CR.sub.10 R.sub.20).sub.n 'OR.sub.9, heterocyclyl, heterocyclylC.sub.1-10 alkyl, C.sub.1-10 alkyl, halo-substituted C.sub.1-10 alkyl, C.sub.2-10 alkenyl, C.sub.2-10 alkynyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkylC.sub.1-10 alkyl, C.sub.5-7 cycloalkenyl, C.sub.5-7 cycloalkenyl-C.sub.1-10 -alkyl, aryl, arylC.sub.1-10 alkyl, heteroaryl, heteroaryl-C.sub.1-10 -alkyl, (CR.sub.10 R.sub.20).sub.n OR.sub.11, (CR.sub.10 R.sub.20).sub.n S(O).sub.m R.sub.18, (CR.sub.10 R.sub.20).sub.n NHS(O).sub.2 R.sub.18, (CR.sub.10 R.sub.20).sub.n NR.sub.13 R.sub.14, (CR.sub.10 R.sub.20).sub.n NO.sub.2, (CR.sub.10 R.sub.20).sub.n CN, (CR.sub.10 R.sub.20).sub.n 'SO.sub.2 R.sub.18, (CR.sub.10 R.sub.20).sub.n S(O).sub.m 'NR.sub.13 R.sub.14, (CR.sub.10 R.sub.20).sub.n C(Z)R.sub.11, (CR.sub.10 R.sub.20).sub.n OC(Z)R.sub.11, (CR.sub.10 R.sub.20).sub.n C(Z)OR.sub.11, (CR.sub.10 R.sub.20).sub.n C(Z)NR.sub.13 R.sub.14, (CR.sub.10 R.sub.20).sub.n C(Z)NR.sub.11 OR.sub.9, (CR.sub.10 R.sub.20).sub.n NR.sub.10 C(Z)R.sub.11, (CR.sub.10 R.sub.20).sub.n NR.sub.10 C(Z)NR.sub.13 R.sub.14, (CR.sub.10 R.sub.20).sub.n N(OR.sub.6)C(Z)NR.sub.13 R.sub.14, (CR.sub.10 R.sub.20).sub.n N(OR.sub.6)C(Z)R.sub.11, (CR.sub.10 R.sub.20).sub.n C(.dbd.NOR.sub.6)R.sub.11, (CR.sub.10 R.sub.20).sub.n NR.sub.10 C(.dbd.NR.sub.19)NR.sub.13 R.sub.14, (CR.sub.10 R.sub.20).sub.n OC(Z)NR.sub.13 R.sub.14, (CR.sub.10 R.sub.20).sub.n NR.sub.10 C(Z)NR.sub.13 R.sub.14, (CR.sub.10 R.sub.20).sub.n NR.sub.10 C(Z)OR.sub.10, 5-(R.sub.18)-1,2,4-oxadizaol-3-yl or 4-(R.sub.12)-5-(R.sub.18 R.sub.19)-4,5-dihydro-1,2,4-oxadiazol-3-yl; wherein the aryl, arylalkyl, heteroaryl, heteroaryl alkyl, heterocyclic and heterocyclic alkyl groups are unsubstituted or substituted;n is an integer having a value of 1 to 10;n' is 0, or an integer having a value of 1 to 10;Z is oxygen or sulfur;R.sub.6 is hydrogen, a pharmaceutically acceptable cation, C.sub.1-10 alkyl, C.sub.3-7 cycloalkyl, aryl, arylC.sub.1-4 alkyl, heteroaryl, heteroarylalkyl, heterocyclyl, aroyl, or C.sub.1-10 alkanoyl;R.sub.9 is hydrogen, --C(Z)R.sub.11 or optionally substituted C.sub.1-10 alkyl, S(O).sub.2 R.sub.18, unsubstituted or substituted aryl or unsubstituted or substituted aryl-C.sub.1-4 alkyl;R.sub.10 and R.sub.20 is each independently selected from hydrogen or C.sub.1-4 alkyl;R.sub.11 is hydrogen, C.sub.1-10 alkyl, C.sub.3-7 cycloalkyl, heterocyclyl, heterocyclyl C.sub.1-10 alkyl, aryl, arylC.sub.1-10 alkyl, heteroaryl or heteroaryl C.sub.1-10 alkyl;R.sub.12 is hydrogen or R.sub.16 ;R.sub.13 and R.sub.14 is each independently selected from hydrogen or optionally substituted C.sub.1-4 alkyl, unsubstituted or substituted aryl or unsubstituted or substituted aryl-C.sub.1-4 alkyl, or together with the nitrogen to which they are attached form a heterocyclic ring of 5 to 7 members which ring contains or does not contain an additional heteroatom selected from oxygen, sulfur or NR.sub.9 ;R.sub.15 is R.sub.10 or C(Z)C.sub.1-4 alkyl;R.sub.16 is C.sub.1-4 alkyl, halo-substituted-C.sub.1-4 alkyl, or C.sub.3-7 cycloalkyl;R.sub.18 is C.sub.1-10 alkyl, C.sub.3-7 cycloalkyl, heterocyclyl, aryl, arylalkyl, heterocyclyl, heterocyclyl-C.sub.1-10 alkyl, heteroaryl or heteroarylalkyl; andR.sub.19 is hydrogen, cyano, C.sub.1-4 alkyl, C.sub.3-7 cycloalkyl or aryl;R.sub.21 is alkyl, aryl, arylC.sub.1-6 alkyl, heterocyclic, heterocyclylC.sub.1-6 alkyl, heteroaryl, heteroarylC.sub.1-6 alkyl, wherein each of these moieties are substituted or unsubstituted;which process comprises:a) reacting a compound of the formula ##STR28## wherein R.sub.b is alkyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, arylalkyl, heteroarylalkyl, heterocyclic, or heterocyclicalkyl, all of which are unsubstituted or substituted;R is as defined for Formula (I); andR.sub.2 and R.sub.4 are defined as for Formula (I);with a compound of the formula ##STR29## wherein Z.sub.1 is N(R.sup.d).sub.2, SR.sup.e, OR.sup.e, or R.sup.d ;R.sup.d is independently hydrogen, alkyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, arylalkyl, heteroarylalkyl, heterocyclic, or heterocyclicalkyl, all of which are unsubstituted or substituted;R.sup.e is alkyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, arylalkyl, heteroarylalkyl, heterocyclic, or heterocyclicalkyl, all of which are unsubstituted or substituted; andY is O, S, or NH;to yield a compound of Formula (I), or pharmaceutically acceptable salt thereof.