Pictet–Spengler method for building a dihydroisoquinoline ring. Thus,
treatment of the benzamide ( 61 ) from 2-phenethylamine with phosphorus
oxychloride probably results in initial formation of a transient enol chlor-
ide; this then cyclizes to 62 under reaction conditions. The imine is then
reduced with sodium borohydride 63. Resolution by means of the tartrate
salt affords 64 in optically pure form. Acylation of this intermediate with
ethyl chloroformate leads to carbamate 64. Reaction of 64 with the anion
from chiral quiniclidol ( 65 ) interestingly results in the equivalent of
an ester interchange. Thus, the anticholinergic agent solifenacin ( 66 )
is obtained.^12
Addition of the terpene, farnesol, to cysteine residues near the end of
protein chains is a crucial process for transporting some proteins to the
intended membrane compartment. This process thus plays an important
role in cell proliferation. Inhibitors of the enzyme that catalyzes farnesyla-
tion, farnesyl transferase, provide yet one more mechanism for interrupting
the multiplication of malignant cells. One of several synthesis of this agent
HN
CH 3COClCl+(^6768)
Cl
O N
CH 3
PPA
O N
CH 3
Cl
O N
CH 3
Cl
Cl
ClOC
Cl
N O
N
BuLi
O N
CH 3
Cl
R
N
N
CH 3 CH 3
(^6970)
72 ; R = OH 71
73 ; R = NH 2
- Br 2
starts with the acylation ofN-methylaniline ( 68 ) with the cinnamoyl chlor-
ide ( 67 ). Treatment of the resulting amide ( 69 ) with polyphosphoric acid
leads to attack of the protonated olefin onto the adjacent benzene ring
with formation of the tetrahydroquinolone ( 70 ). This intermediate is then
reacted with 4-chlorobenzoyl chloride in the presence of a Friedel–
Crafts catalyst to afford the corresponding ketone. The heterocyclic ring
is next dehydrogenated by reaction with bromine. The initially formed
- COMPOUNDS WITH ONE HETEROATOM 171