Patent ID: 6093821
Filing Date: 2000-07-25
Classification: C07D

Abstract:
A method of producing a 6-substituted-1,2-dihydro N-1 protected quinoline comprising:(a) in a one-pot reaction, exchanging a 6-halo-1,2-dihydro N-1 protected quinoline of the formula: ##STR85## in the presence of an alkyllithium, followed by addition of an organoborate and acid treatment to yield the corresponding 6-boro-1,2-dihydro N-1 protected quinoline;(b) coupling the 6-boro-1,2-dihydro N-1 protected quinoline with a coupling partner of the formula RY' in the presence of palladium catalyst and base to yield a 6-substituted-1,2-dihydro N-1 protected quinoline of the formula: ##STR86## wherein R.sup.3 is hydrogen, a C.sub.1 -C.sub.4 alkyl, aryl or heteroaryl; R.sup.9 and R.sup.10 each independently are a C.sub.1 -C.sub.4 alkyl, aryl or heteroaryl; R.sup.4 through R.sup.6 each independently are hydrogen, a C.sub.1 -C.sub.4 alkyl, optionally substituted allyl, aryl methyl, alkenyl, alkynyl, aryl, heteroaryl, HOCH.sub.2, F, Cl, Br, I, cyano, R.sup.2 R.sup.7 N or C.sub.1 -C.sub.4 perfluoroalkyl, where R.sup.2 and R.sup.7 each independently are hydrogen, a C.sub.1 -C.sub.4 alkyl, optionally substituted allyl, arylmethyl, aryl or heteroaryl; R is a phenyl or heteroaryl, where said R heteroaryl is attached through a carbon or nitrogen atom; X' is Br, Cl or I; Y' is Cl, Br, I or OSO.sub.2 CF.sub.3 ; and P is hydrogen, a C.sub.1 -C.sub.6 alkyl, optionally substituted allyl, arylmethyl, aryl or heteroaryl, R.sup.34 C.dbd.O, R.sup.34 C.dbd.S, R.sup.35 OC.dbd.O, R.sup.35 SC.dbd.O, R.sup.35 OC.dbd.S, R.sup.35 SC.dbd.S or R.sup.35 R.sup.36 NC.dbd.O, where R.sup.34 is hydrogen, a C.sub.1 -C.sub.6 alkyl or perfluoroalkyl, optionally substituted allyl or aryl methyl, alkenyl, alkynyl, aryl or heteroaryl, and where R.sup.35 and R.sup.36 each independently are hydrogen, a C.sub.1 -C.sub.6 alkyl, optionally substituted allyl, arylmethyl, aryl or heteroaryl, except that P cannot be H when R.sup.3 is H, or when R is unsubstituted phenyl (C.sub.6 H.sub.5), or when R is phenyl and R.sup.3, R.sup.9 and R.sup.10 are all methyl, and P cannot be R.sup.34 C.dbd.O when R.sup.3 is H and R.sup.34 is pyrazinyl or 3-pyridyl.