Organic Chemistry of Drug Synthesis. Volume 7

Displacement of that halogen by the amine on the aniline ( 170 ) adds the
final ring affording 171.^25

N

CH 3 O N

HO

O

163

OCOC(CH^3 )^3

+ N

OH

tBuOCO

164

Ph 3 P

DEAD N

CH 3 O N

O

OCOC(CH^3 )^3

N

O

R

165 ; R = tBuOCO

166 ; R = H

HCHO

NaB(OAc) 3 H

N

N

CH 3 O

O

OCOC(CH^3 )^3

N

O

H 3 C 167

NH 3

N

CH 3 O NH

O

N

O

H 3 C 168

SO 2 Cl

N

CH 3 O N

Cl

N

O

H 3 C 169

F Br

H 2 N

F Br

170 N

CH 3 O N

N

O

H 3 C 171

HN

The structures of two recent quinazoline kinase inhibitors feature a
somewhat different substitution pattern from the preceding compounds.
Lapatinib( 182 ), for example, features single side chain on the fused
benzene ring; that group is, however, more complex than those in the
earlier examples. Preparation of the ring that will attach at the 1 position

N

NH

O

I

N

N

Cl

I

176

O 2 N

Cl OH

Br F

172 173

+

1. K 2 CO 3
   R 2 N

Cl O F

174 ; R = O

175 ;R = H^177

N

I N

HN

Cl O F

178

PdOAc 2 Ph 3 P

O = HC O B(OH) 2

179

N

N

HN

Cl O F

O = HC O

180

182 SIX-MEMBERED HETEROCYCLES FUSED TO ONE BENZENE RING