substituent to the fused heterocyclic ring ( 77 ). The methyl group at the 2
position on this ring is next oxidized with NBS and benzoyl peroxide to
yield aldehyde 78. Reaction of 78 with nitromethane in the presence of
ammonium acetate extends the chain by one carbon ( 79 ). Treatment with
zinc amalgam and acid reduces both the nitro group and the double
bond to afford the derivative with an ethylamine side chain ( 80 ).
Acylation of that basic nitrogen with the benzylsulfonyl chloride 81 fol-
lowed by saponification of the methyl ester affords the phospholipase
inhibitor 82.^11
CO 2 CH 3HO
72Br
H 3 CO OCH 3+73K 2 CO 3CO 2 CH 3O
H 3 CO OCH 3
NHEt 3 Si
CF 3 CO 2 HCO 2 CH 3CH 3
74
76
(CNaH 6 H 5 ) 2 CBrNCH 3NBS
C 6 H 5 CO 3 H
N
N CH^3 NO^2 CH=ONO 279 78 77Zn(Hg0)H 3 O+NNH 2 1. ClO^2 S- NaOH N
NH Cl
SO 280 8281ClCl Cl
ClCl ClNHCl CH
3(^75) O
O CO 2 CH (^3) O CO 2 CH 3 O CO 2 CH 3
O CO 2 CH (^3) O CO 2 CH 3
Cl
Cl
Cl
C. Indolones
As noted earlier tyrosine kinases play a major role in cell proliferation
tyrosine kinases comprises a major theme in the search for antitumor
148 FIVE-MEMBERED HETEROCYCLES FUSED TO ONE BENZENE RING