Process for pyrimidinone compounds

This invention relates to a process for the preparation of pyrimidinone compounds of the formula ##STR1## wherein Ar is an optionally substituted aryl or heteroaromatic moiety, PA1 R.sup.3 is an optionally substituted alkyl, alkenyl or alkynyl, PA1 R.sup.5 is a hydrogen atom, halo, cyano or an optionally substituted alkyl, alkenyl, alkynyl, alkoxy or alkylthio, and PA1 R.sup.6 is a hydrogen atom, cyano, or an optionally substituted alkyl, cycloalkyl, alkenyl, alkynyl, aryl, aralkyl or heteroaryl. The process comprises reaction of an amidine and a malonic acid derivative to give a hydroxypyrimidinone followed by conversion of the resulting hydroxypyrimidinone to a sulfonyloxypyrimidinone followed by reaction of the resulting sulfonyloxypyrimidinone with an organometallic reagent to give the desired pyrimidinone. The hydroxypyrimidinones, wherein R.sup.6 is hydroxy and sulfonyloxypyrimidinones wherein R.sup.6 is a substituted sulfonyloxy moiety, are themselves new and useful intermediates in the preparation of the desired pyrimidinones.

This is a nonprovisional application of prior pending provisional 
application Ser. No. 60/015,244 filed Apr. 10, 1996 
This invention relates to a process for the preparation of pyrimidinone 
compounds. The process comprises reaction of an amidine and a malonic acid 
derivative to give a hydroxypyrimidinone followed by conversion of the 
resulting hydroxypyrimidinone to a sulfonyloxypyrimidinone followed by 
reaction of the resulting sulfoinyloxypyrimidinone with an organometallic 
reagent to give the desired pyrimidinone. The pyrimidinone compounds 
produced by the process of the present invention are very useful as 
herbicidal agents for the control of weeds in agronomically important 
crops. Such uses are disclosed in both U.S. Pat. No. 5,300,477 and U.S. 
Pat. No. 5,453,414. 
Existing art for preparation of certain pyrimidinone herbicides of formula 
V 
##STR2## 
requires alkylation, for example, propargylation, of a pyrimidinone of 
formula V when R.sup.3 is a hydrogen atom and gives a mixture of N- and 
O-alkylation (propargylation) products that are difficult to separate. 
Often the undesired O-alkylated (propargylated) product predominates. The 
method of the present invention completely avoids this selectivity problem 
through the use of a different chemical process. 
One of the intermediates of formula III in the process of this invention is 
##STR3## 
disclosed in both Chem. Abstr. 60: 9276d and Chem. Abstr. 59: 11524h 
wherein Ar is phenyl, R.sup.3 is ethyl and R.sup.5 is a hydrogen atom. 
However, the process used in both these references employs the reaction of 
carbon suboxide with N-ethylbenzamidine. The references neither disclose 
nor suggest the process of the present invention. 
One embodiment of the process of the present invention to make a 
pyrimidinone compound of formula V 
##STR4## 
comprises the steps of (i) reacting an N-substituted amidine of formula I 
with an activated malonic acid derivative of formula II at room 
temperature or below in the presence of a base and a solvent or solvent 
mixture to form a hydroxypyrimidinone compound of formula III 
##STR5## 
(ii) reacting the resulting hydroxypyrimidinone compound of formula III 
with a compound of the formula RfSO.sub.2 Z to form a 
sulfonyloxypyrimidinone compound of formula IV 
##STR6## 
(iii) reacting the resulting sulfonyloxypyrimidinone compound of formula 
IV with an organometallic reagent of the formula R.sup.6 M, in the 
presence or absence of catalysts, a base and other additives, at a 
temperature from about -80.degree. C. to about 150.degree. C. in a solvent 
or mixture of solvents to form a pyrimidinone compound of formula V 
wherein 
Ar is a (C.sub.6 -C.sub.10)aryl or (C.sub.4 -C.sub.5)heteroaromatic group, 
or a (C.sub.6 -C.sub.10)aryl or (C.sub.4 -C.sub.5)heteroaromatic group 
substituted with up to three substituents independently selected from 
bromo, chloro, fluoro, (C.sub.1 -C.sub.12)alkyl, cyclo(C.sub.3 
-C.sub.8)alkyl, (C.sub.2 -C.sub.12)alkenyl, cyclo(C.sub.3 
-C.sub.8)alkenyl, (C.sub.2 -C.sub.12)alkynyl, halo(C.sub.1 
-C.sub.12)alkyl, halo(C.sub.2 -C.sub.12)alkenyl, halo(C.sub.2 
-C.sub.12)alkynyl, (C.sub.1 -C.sub.12)alkoxy, (C.sub.1 
-C.sub.12)alkylthio, (C.sub.1 -C.sub.12)alkylsulfonyl, (C.sub.1 
-C.sub.12)alkylsulfinyl, phenyl, phen(C.sub.1 -C.sub.12)alkyl, 
phen(C.sub.2 -C.sub.12)alkenyl, phen(C.sub.2 -C.sub.12)alkynyl, cyano, 
halo(C.sub.1 -C.sub.12)alkoxy, 1,3-dioxalan-2-yl, alkylenedioxy and nitro; 
R.sup.3 is a (C.sub.1 -C.sub.6)alkyl, (C.sub.3 -C.sub.6)alkenyl, (C.sub.3 
-C.sub.6)alkynyl, (C.sub.1 -C.sub.6)alkoxy(C.sub.2 -C.sub.6)alkyl, or 
silyl(C.sub.3 -C.sub.6)alkynyl of the form (CH.sub.2).sub.n 
C.tbd.-CSiR.sup.a R.sup.b R.sup.c wherein n is 1, 2, 3 or 4 and R.sup.a, 
R.sup.b, and R.sup.c are independently selected from (C.sub.1 
-C.sub.6)alkyl and phenyl; or is a (C.sub.1 -C.sub.6)alkyl, (C.sub.3 
-C.sub.6)alkenyl, (C.sub.3 -C.sub.6)alkynyl, (C.sub.1 
-C.sub.6)alkoxy(C.sub.2 -C.sub.6)alkyl, or silyl(C.sub.3 -C.sub.6)alkynyl 
of the form (CH.sub.2).sub.n C.tbd.CSiR.sup.a R.sup.b R.sup.c wherein n is 
1, 2, 3 or 4 and R.sup.a, R.sup.b, and R.sup.c are independently selected 
from (C.sub.1 -C.sub.6)alkyl and phenyl, wherein each of the foregoing 
groups is substituted with up to five halogen atoms; 
R.sup.5 is a hydrogen atom, (C.sub.1 -C.sub.6)alkyl, (C.sub.3 
-C.sub.6)alkenyl, (C.sub.3 -C.sub.6)alkynyl, (C.sub.1 -C.sub.6)alkoxy, 
halo(C.sub.1 -C.sub.6)alkyl, halo(C.sub.2 -C.sub.6)alkenyl, halo(C.sub.2 
-C6)alkynyl, halo(C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.6)alkylthio, a 
halogen atom or cyano; 
R.sup.6 is a hydrogen atom, (C.sub.1 -C.sub.12)alkyl, cyclo(C.sub.3 
-C.sub.7)alkyl, (C.sub.2 -C.sub.2)alkenyl, (C.sub.2 -C.sub.12)alkynyl, 
halo(C.sub.1 -C.sub.6)alkyl, halo(C.sub.2 -C.sub.6)alkenyl, halo(C.sub.2 
-C.sub.6)alkynyl, tri(C.sub.1 -C.sub.6)alkylsilyl(C.sub.2 
-C.sub.12)alkynyl, cyano, (C.sub.6 -C.sub.10)aryl, ar(C.sub.1 
-C.sub.4)alkyl, (C.sub.4 -C.sub.5)heterocyclyl, or (C.sub.6 
-C.sub.10)aryl, ar(C.sub.1 -C.sub.4)alkyl or (C.sub.4 
-C.sub.5)heterocyclyl substituted on the aryl portion with up to three 
substituents independently selected from bromo, chloro, fluoro, (C.sub.1 
-C.sub.12)alkyl, cyclo(C.sub.3 -C.sub.8)alkyl, (C.sub.2 -C.sub.12)alkenyl, 
cyclo(C.sub.3 -C.sub.8)alkenyl, (C.sub.2 -C.sub.12)alkynyl, halo(C.sub.1 
-C.sub.12)alkyl, halo(C.sub.2 -C.sub.12)alkenyl, halo(C.sub.2 
-C.sub.6)alkynyl, (C.sub.1 -C.sub.12)alkoxy, (C.sub.1 -C.sub.12)alkylthio, 
(C.sub.1 -C.sub.12)alkylsulfonyl, (C.sub.1 -C.sub.12)alkylsulfinyl, 
phenyl, phen(C.sub.1 -C.sub.12)alkyl, phen(C.sub.2 -C.sub.12)alkenyl, 
phen(C.sub.2 -C.sub.12)alkynyl, cyano, halo(C.sub.1 -C.sub.12)alkoxy, 
1,3-dioxalan-2-yl, and nitro; 
X and Y are both good leaving groups; 
Z is fluoro, chloro or OSO.sub.2 Rf; 
Rf is perfluoro(C.sub.1 -C.sub.12)alkyl or fluoro; and 
R.sup.6 M is an organometallic reagent wherein M is selected from lithium, 
copper, aluminum, magnesium, zinc, tin, silicon, boron and combinations 
thereof. 
The groups such as alkyl, alkenyl, alkynyl, alkoxy, alkylthio and the like 
as well as other moieties containing these groups, such as aralkyl, 
alkoxyalkyl, alkylsulfonyl and the like, described hereinabove and below 
can be either a straight chain such as n-propyl or a branched chain such 
as isobutyl or tert-butyl. The prefix halo in such groups, such as 
haloalkyl, haloalkoxy and the like, can represent monohalo, polyhalo in 
which the halogen atoms can be the same or different, or perhalo. 
In a preferred embodiment, the process of the present invention leading to 
a pyrimidinone compound of formula V comprises the steps of 
(i) reacting an N-substituted amidine of formula I with an activated 
malonic acid derivative of formula II from about -40.degree. C. to about 
-80.degree. C. in the presence of an amine or an amide base and an ether, 
hydrocarbon, chlorinated hydrocarbon or a nitrile solvent or a mixture 
thereof to form a hydroxypyrimidinone compound of formula III, 
(ii) reacting the resulting hydroxypyrimidinone compound III with a 
compound of the formula RfSO.sub.2 Z to form a sulfonyloxypyrimidinone 
compound of formula IV and 
(iii) reacting the resulting sulfonyloxypyrimidinone compound of formula IV 
with an organometallic reagent of the formula R.sup.6 M, in the presence 
or absence of catalysts, a base and other additives, at a temperature from 
about -80.degree. C. to about 150.degree. C. in a solvent or a mixture of 
solvents to form a pyrimidinone compound of formula V wherein 
Ar is furyl, naphthyl, phenyl, pyridyl, pyridyl salt or thienyl, or furyl, 
naphthyl, phenyl, pyridyl, pyridyl salt or thienyl substituted with up to 
three substituents independently selected from bromo, chloro, fluoro, 
(C.sub.1 -C.sub.6)alkyl, cyclo(C.sub.5 -C.sub.6)alkyl, (C.sub.2 
-C.sub.6)alkenyl, cyclo(C.sub.3 -C.sub.8)alkenyl, (C.sub.2 
-C.sub.6)alkynyl, halo(C.sub.1 -C.sub.6)alkyl, halo(C.sub.2 
-C.sub.6)alkenyl, halo(C.sub.2 -C.sub.6)alkynyl, (C.sub.1 -C.sub.6)alkoxy, 
(C.sub.1 -C.sub.6)alkylthio, (C.sub.1 -C.sub.12)alkylsulfonyl, (C.sub.1 
-C.sub.12)alkylsulfinyl, phenyl, phen(C.sub.1 -C.sub.12)alkyl, 
phen(C.sub.2 -C.sub.12)alkenyl, phen(C.sub.2 -C.sub.12)alkynyl, cyano, 
halo(C.sub.1 -C.sub.6)alkoxy, 1,3-dioxalan-2-yl, methylenedioxy, 
1,2-ethylenedioxy and nitro; 
R.sup.3 is methyl, ethyl, n-propyl, (C.sub.3 -C.sub.4)alkenyl, (C.sub.3 
-C.sub.6)alk-2-ynyl, (C.sub.1 -C.sub.2)alkoxy(C.sub.2 -C.sub.3)alkyl, 
3-(trimethylsilyl)prop-2-ynyl, 3-(tert-butyldimethylsilyl)prop-2-ynyl or 
3-(phenyldimethylsilyl)prop-2-ynyl, or is methyl, ethyl, n-propyl, 
(C.sub.3 -C.sub.4)alkenyl, (C.sub.3 -C.sub.6)alk-2-ynyl, (C.sub.1 
-C.sub.2)alkoxy(C.sub.2 -C.sub.3)alkyl, 3-(trimethylsilyl)prop-2-ynyl, 
3-(tert-butyldimethylsilyl)prop-2-ynyl or 
3-(phenyldimethylsilyl)prop-2-ynyl wherein each of the foregoing groups is 
substituted with up to five halogen atoms; 
R.sup.5 is a hydrogen atom, chloro, fluoro, methyl, ethyl, n-propyl, 
isopropyl, allyl, prop-2-ynyl, (C.sub.1 -C.sub.2)alkoxy, C.sub.1 
-C.sub.2)alkylthio, halo(C.sub.1 -C.sub.2)alkyl or halo(C.sub.1 
-C.sub.2)alkoxy; 
R.sup.6 is a hydrogen atom, (C.sub.1 -C.sub.6)alkyl, cyclopropyl, 
cyclobutyl, cyclopentyl, (C.sub.2 -C.sub.6)alkenyl, (C.sub.2 
-C.sub.6)alkynyl, halo(C.sub.1 -C.sub.3)alkyl, halo(C.sub.2 
-C.sub.6)alkenyl, halo(C.sub.2 -C.sub.6)alkynyl, tri(C.sub.1 
-C.sub.6)alkylsilyl(C.sub.2 -C.sub.12)alkynyl, cyano, phenyl, benzyl, 
2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl or 4-pyridyl, 
or phenyl, benzyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 
3-pyridyl or 4-pyridyl substituted on the aryl portion with up to three 
substituents independently selected from bromo, fluoro, fluoro, (C.sub.1 
-C.sub.6)alkyl, cyclo(C.sub.5 -C.sub.6)alkyl, (C.sub.2 -C.sub.6)alkenyl, 
cyclo(C.sub.3 -C.sub.8)alkenyl, (C.sub.2 -C.sub.6)alkynyl, halo(C.sub.1 
-C.sub.6)alkyl, halo(C.sub.2 -C.sub.6)alkenyl, halo(C.sub.2 
-C.sub.6)alkynyl, (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.6)alkylthio, 
(C.sub.1 -C.sub.12)alkylsulfonyl, (C.sub.1 -C.sub.12)alkylsulfinyl, 
phenyl, phen(C.sub.1 -C.sub.12)alkyl, phen(C.sub.2 -C.sub.12)alkenyl, 
phen(C.sub.2 -C.sub.12)alkynyl, cyano, halo(C.sub.1 -C.sub.6)alkoxy, 
1,3-dioxalan-2-yl and nitro; 
X and Y are independently selected from chloro, carboxylate and 
1-imidazolyl; 
Z is fluoro, chloro or OSO.sub.2 Rf; 
Rf is perfluoro(C.sub.1 -C.sub.4)alkyl or fluoro; and 
R.sup.6 M is an organometallic reagent selected from (R.sup.6).sub.2 
CuCNLi.sub.2, (R.sup.6).sub.3 B and R.sup.6 SnR.sup.x R.sup.y R.sup.z 
wherein R.sup.x, R.sup.y and R.sup.z are alkyl. 
In step (i) of this preferred embodiment, preferred bases are 
triethylamine, N-methylmorpholine, lithium diisopropylamide and sodium 
bis(trimethylsilyl)amide. The most preferred base is sodium 
bis(trimethylsilyl)amide. Preferred solvents are tetrahydrofuran (THF), 
diethyl ether, dioxane, dimethoxymethane, toluene, dichloromethane and 
acetonitrile. THF is the most preferred solvent. 
In step (ii) of this preferred embodiment, trifluoromethanesulfonic 
anhydride is a preferred reactant to convert a hydroxypyrimidinone 
compound of formula III to a sulfonyloxypyrimidinone compound of formula 
IV. 
In step (iii) of this preferred embodiment, when the organometallic reagent 
is a higher order cuprate such as (R.sup.6).sub.2 CuCNLi.sub.2, no 
catalyst is employed and preferred temperatures are from about -80.degree. 
C. to about -40.degree. C. and THF is a preferred solvent. When the 
organometallic reagent is a borane or tin compound, preferred catalysts 
include palladium and nickel compounds such as 
tetrakis(triphenylphosphine)palladium0!, 
1,1'-bis(diphenylphosphino)ferrocene!palladiumII! chloride, 
tris(dibenzylideneacetone)dipalladium0!, 
bis(benzonitrile)dichloropalladiumII!, 
dichlorobis(triphenylphosphine)palladiumII! and 
1,3-bis(diphenylphosphino)propane!nickelII! chloride. Preferred bases 
include alkali metal carbonates, alkali metal phosphates, thallium 
carbonate and silver oxide. A preferred additive is lithium chloride or 
potassium bromide. Preferred solvents and temperatures are dioxane, THF, 
diethyl ether, benzene, dimethylformamide (DMF) and 
N-methyl-2-pyrrolidinone (NMP) or mixtures thereof from about 20.degree. 
C. to about the boiling point of the solvent or 150.degree. C., whichever 
is lower. 
In some cases the compound of formula IV is partly or completely reduced by 
the organometallic reagent to produce the pyrimidinone of formula V 
wherein R.sup.6 is a hydrogen atom. 
In a more preferred embodiment, the process of the present invention is 
used to produce pyrimidinones of formula V wherein 
Ar is 2-furyl, 3-furyl, 4-chloro-2-furyl, 5-chloro-2-furyl, 
5-chloro-3-furyl, 2,5-dichloro-3-furyl, 2-naphthyl, phenyl, 
3-methylphenyl, 3-methoxyphenyl, 3-nitrophenyl, 4-fluorophenyl, 
4-chlorophenyl, 3-trifluoromethylphenyl, 3-bromophenyl, 3-chlorophenyl, 
3-fluorophenyl, 3-trifluoromethoxyphenyl, 3-cyanophenyl, 
3-(1,3-dioxolan-2-yl)phenyl, 2-fluorophenyl, 2-chlorophenyl, 
2-trifluoromethoxyplhenyl, 3,5-difluorophenyl, 3,5-dichlorophenyl, 
2,4-difluorophenyl, 2,5-difluorophenyl, 3-chloro-4-fluorophenyl, 
3,4-difluorophenyl, 3-fluoro-5-trifluoromethylphenyl, 
3,4,5-trifluorophenyl, 2-pyridyl, 4-chloro-2-pyridyl, 6-chloro-2-pyridyl, 
4,6-dichloro-2-pyridyl, 3-pyridyl, 5-bromo-3-pyridyl, 
5,6-dichloro-3-pyridyl, 5-chloro-3-pyridyl, 5-fluoro-3-pyridyl, 4-pyridyl, 
2-fluoro-4-pyridyl, 2-chloro-4-pyridyl, 2-chloro-6-methyl-4-pyridyl, 
2-methyl-4-pyridyl, 2-methoxy-4-pyridyl, 2-cyano-4-pyridyl, 
2,6-difluoro-4-pyridyl, 2,6-dichloro-4-pyridyl, 2-thienyl, 3-thienyl, 
4-chloro-2-thienyl, 5-chloro-2-thienyl, 5-chloro-3-thienyl, 
2,5-dichloro-3-thienyl or 3,4-methylenedioxyphenyl; 
R.sup.3 is ethyl, allyl, 3-chloroallyl, prop-2-ynyl, but-2-ynyl, 
pent-2-ynyl or 2-methoxyethyl; 
R.sup.5 is methyl, ethyl, methoxy, methylthio, difluoromethoxy or 
trifluoromethoxy; and 
R.sup.6 is methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, sec-butyl, 
isopropyl, isobutyl, vinyl, isopropenyl, allyl, ethynyl, prop-1-ynyl, 
1-methylprop-2-ynyl, prop-2-ynyl, trifluoromethyl, pentafluoroethyl, 
trichloromethyl, bromomethyl, chloromethyl, difluoromethyl, 
chlorodifluoromethyl, phenyl or 3-thienyl. 
In another embodiment of this invention, when R.sup.6 is a 1-alkynyl group, 
the alkyne R.sup.6 H may be used in place of R.sup.6 M in the presence of 
a catalyst and in the presence of a base from about 20.degree. C. to about 
150.degree. C. in a solvent in process step (iii). A preferred alkyne 
R.sup.6 H is (trimethylsilyl)acetylene, a preferred catalyst is 
dichlorobis(triphenylphosphine)palladiumII!, a preferred base is 
triethylamine and a preferred solvent is DMF. 
In yet another embodiment of this invention, when R.sup.3 in a compound of 
formula IV is a terminal alkynyl group, for example, R.sup.3 is 
(CH.sub.2).sub.n C.tbd.CH wherein n is 1, 2, 3 or 4, the alkyne can be 
protected as a silyl derivative in an intermediate step (iia) by 
deprotonation with a base and reaction with a silylating agent R.sup.a 
R.sup.b R.sup.c SiY' wherein R.sup.a, R.sup.b and R.sup.c are 
independently selected from (C.sub.1 -C.sub.6)alkyl and phenyl and Y' is a 
good leaving group, prior to coupling with the organometallic reagent 
R.sup.6 M in process step (iii). Preferred bases include alkylithiums, 
alkyl magnesiumhalides and alkali metal amides. Preferred silylating 
agents R.sup.a R.sup.b R.sup.c SiY' are silyl chlorides and triflates 
wherein Y' is chloro or trifluoromethanesulfonyloxy. The coupling product 
of formula V, wherein R.sup.3 is (CH.sub.2).sub.n C.tbd.CSiR.sup.a R.sup.b 
R.sup.c, may be deprotected to give a compound of formula V wherein 
R.sup.3 is (CH.sub.2).sub.n C.tbd.CH if desired. 
##STR7## 
The substituent preferences for Ar, R.sup.5 and Rf in the compound of 
formula IVa are the same as those described hereinabove for the compound 
of formula IV. 
In still another embodiment of this invention are compounds of formula III 
which are useful as intermediates in the process of the present invention 
to the herbicidal compounds of formula V wherein Ar and R.sup.5 are the 
same as those described hereinabove for the compound of formula III in the 
process embodiment of the present invention and R.sup.3 is a (C.sub.4 
-C.sub.6)alkyl, (C.sub.3 -C.sub.6)alkenyl, (C.sub.3 -C.sub.6)alkynyl, 
(C.sub.1 -C.sub.6)alkoxy(C.sub.2 -C.sub.6)alkyl, or silyl(C.sub.3 
-C.sub.6)alkynyl of the form (CH.sub.2).sub.n C.tbd.CSiR.sup.a R.sup.b 
R.sup.c wherein n is 1, 2,3 or 4 and R.sup.a, R.sup.b, and R.sup.c are 
independently selected from (C.sub.1 -C.sub.6)alkyl and phenyl; or is a 
(C.sub.4 -C.sub.6)alkyl, (C.sub.3 -C.sub.6)alkenyl, (C.sub.3 
-C.sub.6)alkynyl, (C.sub.1 -C.sub.6)alkoxy(C.sub.2 -C.sub.6)alkyl, or 
silyl(C.sub.3 -C.sub.6)alkynyl of the form (CH.sub.2).sub.n 
C.tbd.CSiR.sup.a R.sup.b R.sup.c wherein n is 1, 2, 3 or 4 and R.sup.a, 
R.sup.b, and R.sup.c are independently selected from (C.sub.1 -C6)alkyl 
and phenyl wherein each of the foregoing groups is substituted with up to 
five halogen atoms. 
In yet still another embodiment of this invention are compounds of formula 
IV which are useful as intermediates in the process of the present 
invention to the herbicidal compounds of formula V wherein Ar, R.sup.3, 
R.sup.5 and Rf are the same as those described hereinabove for the 
compound of formula IV in the process embodiment of the present invention.

The following examples serve only to illustrate the utilization of the 
present invention and are not meant to limit the scope of the present 
invention which is defined by the claims. 
A. EXAMPLES OF CONVERSION OF I AND II TO III 
Example 1 
Preparation of 
2-(2,6-dichloro-4-pyridyl)-5-ethyl-6-hydroxy-3-propargyl-4(3H)-pyrimidinon 
e 
To a cold (-78.degree. C.) solution of 
2,6-dichloropyridine-4-(N-propargyl)carboxamidine (0.228 g, 1.0 mmol) in 5 
mL of THF was added sodium bis(trimethylsilyl)amide (1.0 mL, 1 mmol, 1 
equiv, 1M solution in THF). The reaction mixture was stirred for 10 min at 
-78.degree. C. and a cold (-78.degree. C.) solution of ethylmalonyl 
dichloride (0.186 g, 1.1 mmol, 1.1 equiv) in 5 mL of THF was added via a 
canula over 10 min. The reaction mixture was stirred for 40 min, quenched 
with 10 mL of water and warmed to room temperature. After diluting with 30 
mL of ethyl acetate, the organic layer was successively washed with water 
(10 mL), saturated sodium chloride (10 mL), dried (MgSO.sub.4) and 
concentrated to give a yellow solid. The crude product was purified by 
flash chromatography (silica gel, CH.sub.2 Cl.sub.2 /MeOH, 98/2) to afford 
0.205 g (63%) of 
2-(2,6-dichloro-4-pyridyl)-5-ethyl-6-hydroxy-3-propargyl-4(3H)-pyrimidinon 
e: mp 200.degree.-202.degree. C.; IR (KBr) 3237, 3170, 1623, 1541, 1528, 
1361 cm.sup.-1 ; .sup.1 H NMR (270 MHz, CDCl.sub.3) .delta. 1.11 (t, J=7.6 
Hz, 3H), 2.44-2.54 (m, 3H), 4.59 (d, J=2.3 Hz, 2H), 7.59 (s, 2H), 9.25 (br 
s, 1H); Anal. Calcd for C.sub.14 H.sub.11 Cl.sub.2 N.sub.3 O.sub.2 : C, 
51.87;H, 3.42;N, 12.96. Found: C, 51.67;H, 3.59;N, 12.70. 
Example 2 
Preparation of 
2-(2.6-dichloro-4-pyridyl)-6-hydroxy-5-(1-methylethyl)-3-propargyl-4(3H)-p 
yrimidinone 
A stirred solution of 10.32 g (45.3 mmol) of 
2,6-dichloropyridine-4-(N-propargyl)carboxamidine in 250 mL of dry THF was 
cooled to -70.degree. C. and 50 mL of 1.0M (50.0 mmol) sodium 
bis(trimethylsilyl)amide in THF was added over 10 min. The mixture was 
stirred at -70.degree. C. for 40 min and a solution of 8.47 g (46.3 mmol) 
of isopropylmalonyl dichloride in 50 mL of THF was added dropwise over 40 
min. The mixture was stirred at -70.degree. C. for 40 min and quenched by 
addition of 50 mL of water. The mixture was removed from the cooling bath 
and the bulk of the THF was evaporated under reduced pressure. The residue 
was diluted with 150 mL of 5% aqueous hydrochloric acid and extracted with 
two 200 mL portions of ethyl acetate. The combined organic layers were 
washed with 50 mL of brine and dried over MgSO.sub.4. Removal of the 
solvent under reduced pressure afforded 15.65 g of crude 
2-(2,6-dichloro-4-pyridyl)-6-hydroxy-5-(1-methylethyl)-3-propargyl-4(3H)-p 
yrimidinone-as a viscous oil. .sup.1 H NMR (CDCl.sub.3) .delta. 1.25 (d, 
6H), 2.45 (t, 1H), 3.3 (m, 1H), 4.55 (d, 2H), 7.6 (s, 2H). This material 
was used without further purification. 
Example 3 
Preparation of 
2-(2.6-dichloro-4-pyridyl)-6-hydroxy-5-methoxy-3-propargyl-4(3H)-pyrimidin 
one 
A stirred solution of 52.44 g (0.23 mol) of 
2,6-dichloropyridine-4-(N-propargyl)carboxamidine in 600 mL of dry THF, 
under a nitrogen atmosphere, was cooled to -70.degree. C. and 242.6 mL 
(0.24 mol) of 1.0M sodium bis(trimethylsilyl)amide in THF was added 
dropwise over 1.25 hours, maintaining the temperature at or below 
-70.degree. C. The reaction mixture was stirred an additional 15 minutes 
at -70.degree. C. and a solution of 40 g (0.23 mol) of methoxymalonyl 
dichloride in 100 mL of dry THF was added dropwise over 1.5 hours. The 
mixture was stirred at -70.degree. C. for 30 minutes and quenched by the 
addition of 125 mL of water. The bulk of the THF was removed on the 
rotovap and the residue was taken up in ethyl acetate and 3M HCl. The 
layers were separated and the aqueous layer was extracted four times with 
ethyl acetate. The organic layers were combined and washed once with 3M 
HCl, once with brine, dried over MgSO.sub.4 and concentrated to yield 57 g 
of a golden solid. The product was purified by trituration with a minimal 
amount of CH.sub.2 Cl.sub.2 to yield 5.8g (7.7%) of 
2-(2,6-dichloro-4-pyridyl)-6-hydroxy-5-methoxy-3-propargyl-4(3H)-pyrimidin 
one, as an off white solid. Mp=227.degree.-228.5.degree. C. .sup.1 H NMR 
(d.sub.6 DMSO) .delta. 3.48 (t, 1H), 3.75 (s, 3H), 4.61 (d, 2H) 7.92 (s, 
2H), 11.8 (s, 1H). 
B. EXAMPLES OF PREATION OF IV 
Example 4 
Preparation of 
2-(2.6-dichloro-4-pyridyl)-5-ethyl-3-propargyl-6-trifluoromethanesulfonylo 
xy-4(3H)-pyrimidinone 
To a stirred, cold (-78.degree. C.) solution of 
2-(2,6-dichloro-4-pyridyl)-5-ethyl-6-hydroxy-3-propargyl-4(3H)-pyrimidinon 
e (0.10 g, 0.309 mmol) in 5 mL of dichloromethane was added collidine (0.06 
mL, 0.455 mmol, 1.47 equiv). The reaction mixture was stirred for 5 min 
and trifluoromethanesulfonic anhydride (0.07 mL, 0.417 mmol; 1.35 equiv) 
was added. The reaction mixture was stirred for 30 min at -78.degree. C., 
quenched with 5 mL of water and diluted with 30 mL of CH.sub.2 Cl.sub.2. 
The organic layer was separated, washed with 15 mL of saturated sodium 
chloride, dried (MgSO.sub.4), filtered and concentrated to give a light 
brown oil. The crude product was purified by preparative TLC (ethyl 
acetate/hexane: 2/8) to produce 0.105 g (74%) of 
2-(2,6-dichloro-4-pyridyl)-5-ethyl-3-propargyl-6-trifluoromethanesulfonylo 
xy-4(3H)-pyrimidinone as a white solid: mp 112.degree.-114.degree. C.; IR 
(KBr) 3236, 2125, 1692, 1620, 1555, 1423, 1293, 1201 cm.sup.-1 ; .sup.1 H 
NMR (270 MHz, CDCl.sub.3) .delta. 1.24 (t, J=7.6 Hz, 3H), 2.56 (t, J=2.3 
Hz, 1H), 2.66 (q, J=14.8 Hz, 2H), 4.63 (d, J=2.3 Hz, 2H), 7.66 (s, 2H); 
Anal. Calcd for C.sub.15 H.sub.10 Cl.sub.2 F.sub.3 N.sub.3 O.sub.4 S: C, 
39.49;H, 2.21;N, 9.21. Found: C, 39.69;H, 2.42;N, 9.28. 
Example 5 
Preparation of 
2-(2,6-dichloro-4-pyridyl)-5-(1-methylethyl)-3-propargyl-6-trifluoromethan 
esulfonyloxy-4(3H)-pyrimidinone A stirred solution of 15.65 g of crude 
2-(2,6-dichloro-4-pyridyl)-6-hydroxy-5-(1-methylethyl)-3-propargyl-4(3H)-p 
yrimidinone and 9 mL (77.3 mmol) of 2,6-lutidine in 100 mL of 
dichloromethane was cooled to -70.degree. C. and 12 mL (71.3 mmol) of 
trifluoromethanesulfonic anhydride was added over 2 min. The cooling bath 
was allowed to expire and the mixture was stirred overnight at room 
temperature. The mixture was evaporated under reduced pressure to remove 
dichloromethane. The residue was taken up in 400 mL of ether and washed 
with two 100 mL portions of cold 5% aqueous hydrochloric acid and two 100 
mL portions of cold 5% aqueous NaOH, and dried over MgSO.sub.4. Removal of 
the solvent under reduced pressure afforded 12.64 g of a dark oil. This 
material was purified by flash chromatography on a column of 100 g of 
silica gel which was eluted successively with 250 mL portions of 0, 10, 
20, 30, 40 and 60% ether in hexanes. Fractions of 250 mL were collected. 
Fractions 5 through 9 were combined and concentrated under reduced 
pressure to afford 10.34 g (48%) of 
2-(2,6-dichloro-4-pyridyl)-5-(1-methylethyl)-3-propargyl-6-trifluoromethan 
esulfonyloxy-4(3H)-pyrimidinone as a syrup. .sup.1 H NMR (CDCl.sub.3) 
.delta. 1.35 (d, 6H), 2.55 (t, 1H), 3.3 (m, 1H), 4.6 (d, 2H), 7.7 (s, 2H). 
Example 6 
Preparation of 
2-(2.6-dichloro-4-pyridyl)-5-methoxy-3-propargyl-6-trifluoromethanesulfony 
loxy-4(3H)-pyrimidinone 
A stirred solution of 5.05g (0.015 mol) of 
2-(2,6-dichloropyridyl)-6-hydroxy-5-methoxy-3-propargyl-4(3H)-pyrimidinone 
and 2.9 mL (0.025 mol) of 2,6-lutidine in 100 mL of dichloromethane was 
cooled to -70.degree. C. and 3.9 mL (0.023 mol) of 
trifluoromethanesulfonic anhydride was added dropwise over 30 minutes. The 
mixture was stirred at -70.degree. C. for 30 minutes and allowed to warm 
to room temperature. After 1.5 hours, the mixture was quenched by the 
addition of 50 mL of water. The organic layer was separated and rotovapped 
to remove the dichloromethane. The residue was taken up in ethyl acetate 
and added back to the water layer. 3M HCl was added and the layers were 
separated. The organic layer was washed twice more with 3M HCl. The 
aqueous layers were combined and back extracted once with ethyl acetate. 
The ethyl acetate layers were combined and washed 3 times with saturated 
NaHCO.sub.3, dried over MgSO.sub.4 and concentrated to yield 7.10 g of 
product, as a dark brown solid. The product was triturated with 
dichloromethine and ether to yield a sand colored solid, which was then 
dissolved in ether and dichloromethane and passed through a four inch plug 
of silica gel. The filtrate was concentrated to yield 4.15g of 
2-(2,6-dichloropyridyl)-5-methoxy-3-propargyl-6-trifluoromethanesulfonylox 
y 4(3H)-pyrimidinone, as a white solid, m.p. =133.degree.-135.degree. C. 
The filtrate from the trituration was passed through a plug of silica gel, 
using ether and dichloromethane, and concentrated to yield 2.5 g more of 
the product as a light brown solid. .sup.1 H NMR (CDCl.sub.3) .delta. 
2.6(1H,t), 4.2(3H,s), 4.62(2H,d), 7.65(2H,s). 
Example 7 
Telescoped Preparation of 
5-ethyl-2-phenyl-3-propargyl-6-trifluoromethanesulfonyloxy-4(3H)-pyrimidin 
one from N-propargylbenzamidine and ethylmalonyl dichloride 
To a cold (-78.degree. C.) solution of N-propargylbenzamidine (5.50 g, 
34.77 mmol) in 150 mL of THF was added sodium bis(trimethylsilyl)amide 
(36.51 mL, 36.51 mmol, 1.05 equiv, 1M solution in THF) over 20 minutes. 
The reaction mixture was stirred for 5 minutes at -78.degree. C., followed 
by the addidion of a cold (-78.degree. C.) solution of ethylmalonyl 
dichloride (6.46 g, 38.25 mmol, 1.1 equiv.) in 150 mL of THF via a canula 
over 2 hours. After stirring for 30 minutes, the reaction mixture was 
quenched with 100 mL of water, warmed to room temperature, and diluted 
with 300 mL of ethyl acetate and 100 mL of water. The organic layer was 
successively washed with 200 mL of water and 200 mL of saturated sodium 
chloride, dried (MgSO.sub.4), filtered, and concentrated to give a solid. 
The crude mixture was azeotropically evaporated with 200 mL of toluene to 
remove residual hexamethyldisilazane, affording 8.28 g of 
5-ethyl-6-hydroxy-2-phenyl-3-propargyl-4(3H)-pyrimidinone which was used 
without further purification. 
To a cold (-78.degree. C.) suspension of 6.5 g (25.56 mmol) of the above 
2-phenyl-5-ethyl-6-hydroxy-3-propargyl-4(3H)-pyrimidinone in 150 mL of 
CH.sub.2 Cl.sub.2 was added collidine (5.06 mL, 38.34 mmol, 1.5 equiv) via 
a syringe. The reaction mixture was stirred for 15 minutes, followed by 
the addition of trifluoromethanesulfonic anhydride (6.44 mL, 38.34 mmol, 
1.5 equiv). After stirring for 15 minutes, the reaction mixture-was 
quenched with 100 mL of water, diluted with 250 mL of CH.sub.2 Cl.sub.2, 
and warmed to room temperature. The organic layer was separated, and the 
aqueous layer was extracted with 100 mL of CH.sub.2 Cl.sub.2. The combined 
organic extracts were successively washed with 2.times.100 mL of water, 
2.times.100 mL of saturated sodium chloride, dried (MgSO.sub.4), filtered, 
and concentrated. The crude product was purified by flash chromatography 
(silica gel, ethyl acetate/hexane, 2/8) to afford 4.2 g (42%, based on 
N-propargylbenzamidine) of 5-ethyl-2-phenyl-3-propargyl-6 
-trifluoromethanesulfonyloxy-4(3H)-pyrimidinone: mp 
159.degree.-160.degree. C.; IR (KBr)3281, 2992, 2936, 2133, 1710, 1675, 
1520, 1421, 1196 cm.sup.-1 ; .sup.1 H NMR (270 MHz, CDCl.sub.3) .delta. 
1.24 (t, J=7.3 Hz, 3Ht), 2.46 (t,j=2.3 Hz, 1H), 2.65 (q, J=14.8 Hz, 2H), 
4.64 (d,J=2.3 Hz, 2H), 7.55-7.80 (m, 5H): .sup.13 C NMR (68 MHz, CDCl3) 
.delta. 12.2, 17.8, 37.8, 73.9, 77.6, 116.2, 120.1, 128.7, 129.0, 131.7, 
132.6, 156.7, 158.0, 163.0. Anal. Calcd for C.sub.16 H.sub.13 F.sub.3 
N.sub.2 O.sub.4 S: C, 49.74;H, 3.39;N, 7.25. Found: C, 50.02;H, 3.56;N, 
7.18. 
Example 8 
Preparation of 
5-ethyl-2-phenyl-6-trifluoromethanesulfonyloxy-3-(3-trimethylsilyl)proparg 
yl-4(3H)-pyrimidinone To a stirred, cold (-78.degree. C.) solution of 
5-ethyl-2-phenyl-3-propargyl-6-trifluoromethanesulfonyloxy-4(3H)-pyrimidin 
one (3.0 g, 7.77 mmol) in 75 mL of THF was added n-butyllithium (3.4 mL, 
8.54 mmol, 1.1 equiv, 2.5M in hexane) dropwise. After stirring for 5 
minutes, trimethylsilyl chloride (1.1 mL, 8.54 mmol, 1.1 equiv) was added, 
and the stirring was continued for 30 minutes at -78.degree. C. and 1 hour 
at room temperature. The reaction mixture was quenced with 50 mL of water 
and diluted with 50 mL of ethyl acetate. The two layers were separated and 
the aqueous layer was extracted with 50 mL of ethyl acetate. The combined 
organic layers were washed with 2.times.50 mL of saturated sodium 
chloride, dried (MgSO.sub.4), filtered, and concentrated. The crude 
product was purified by flash chromatography (silica gel, ethyl 
acetate/hexane, 1/9) to afford 2.03 g (56%) of 
5-ethyl-2-phenyl-6-trifluoromethanesulfonyloxy-3-(3-trimethylsilyl)proparg 
yl-4(3H)-pyrimidinone: mp 119.degree.-120.degree. C.; IR (KBr) 2978, 2181, 
1677, 1620, 1518, 1416, 1218, 1200 cm.sup.-1 ; .sup.1 H NMR (270 MHz, 
CDCl.sub.3) .delta. 0.20 (s, 9H) 1.23 (t, J=7.3 Hz, 3H), 2.64 (q, J=14.8 
Hz, 2H), 4.66 (s, 2H), 7.50-7.80 (m, 5H); .sup.13 C NMR (68 MHz, 
CDCl.sub.3) .delta.-0.2, 12.2, 17.9, 38.4, 91.0, 99.0, 116.1, 121.0, 
128.7, 128.8, 131.5, 132.8, 156.7, 158.2, 162.9. Anal. Calcd for C.sub.19 
H.sub.21 F.sub.3 N.sub.2 O.sub.4 SSi:. C, 49.77;H, 4.62;N, 611. Found C, 
49.42;H, 4.34;N, 6.00. 
C. EXAMPLES OF CONVERSION OF IV TO V 
Example 9 
Preparation of 
2-(2,6-dichloro-4-pyridyl)-5-ethyl-6-methyl-3-propargyl-4(3H)-pyrimidinone 
To a stirred, cold (-78.degree. C.) solution of CuCN (1.91 g, 20 mmol) in 
100 mL of THE was added methyllithium (30 mL, 42 mmol, 2.1 equiv, 1.4M in 
diethyl ether) over 10 min. After stirring for 15 min, this solution was 
added over 10 min via a canula to a cold (-78.degree. C.) solution of 
2-(2,6-dichloro-4-pyridyl)-5-ethyl-3-propargyl-6 
-trifluoromethanesulfonyloxy-4(3H)-pyrimidinone in 20 mL of THF. The 
reaction mixture was stirred for 30 min, quenched with 15 mL of 10% 
concentrated NH.sub.4 OH/saturated NH.sub.4 Cl, diluted with 200 mL of 
ethyl acetate and warmed to room temperature. The organic layer was 
separated and the aqueous layer was extracted with ethyl acetate 
(2.times.100 mL). The combined organic layers were dried (MgSO.sub.4), 
filtered and concentrated to give a semi oil. The crude product was 
purified by flash chromatography (silica gel, ethyl acetate/hexane, 2/8) 
to afford 2.29 g (71%) of 
2-(2,6-dichloro-4-pyridyl)-5-ethyl-6-methyl-3-propargyl-4(3H)-pyrimidinone 
as a white solid: mp 143.degree.-144.degree. C.; IR (KBr) 3220, 2125, 
1668, 1584, 1541, 1515, 1367 cm.sup.-1 ; .sup.1 H NMR (270 MHz, 
CDCl.sub.3) .delta. 1.16 (t, J=7.6 Hz, 3H), 2.35 (s, 3H), 2.43 (t, J=2.6 
Hz, 1H), 2.62 (q, J=14.8 Hz, 2H), 4.56 (d, J=2.6 Hz, 2H), 7.60 (s, 2H). 
Example 10 
Preparation of 
2-(2.6-dichloro-4-pyridyl)-5-(1-methylethyl)-3-propargyl-4(3H)-pyrimidinon 
e 
A stirred suspension of 0.65 g (7.3 mmol) of copper(I) cyanide in 20 mL of 
dry THF was cooled to -70.degree. C. and a mixture of 18 mL of 0.85M 
ethyllithium in benzene (15.3 mmol) and 20 mL of ether was added by canula 
over 5 min. The temperature of the mixture rose to -50.degree. C. The 
cooling bath was removed and the mixture was allowed to warm to 
-40.degree. C., then recooled to -70.degree. C. A solution of 1.70 g (3.6 
mmol) of 
2-(2,6-dichloro-4-pyridyl)-5-(1-methylethyl)-3-propargyl-6-trifluoromethan 
esulfonyloxy-4(3H)-pyrimidinone in 12 mL of THF was added rapidly. The 
resulting black mixture was allowed to stir at -70.degree. C. for 40 min 
and poured into 100 mL of 9:1 saturated aqueous NH.sub.4 Cl: concentrated 
NH.sub.4 OH. The mixture was extracted with two 100 mL portions of ether. 
The combined ether extracts were washed with 50 mL of concentrated 
NH.sub.4 OH and dried over MgSO.sub.4. Removal of the solvent under 
reduced pressure afforded 1.66 g of an oil. This material was purified by 
flash chromatography on a column of 30 g of silica gel which was eluted 
successively with 100 mL portions of 0, 10, 20, 30, 40, 50, 60 and 70% 
ether in hexanes. Fractions of 25 mL were collected. Fractions 16 through 
18 were combined and concentrated under reduced pressure to afford 0.42 g 
of 
2-(2,6-dichloro-4-pyridyl)-5-(1-methylethyl)-3-propargyl-4(3H)-pyrimidinon 
e as a syrup. .sup.1 H NMR (CDCl.sub.3) .delta. 1.35 (d, 6H), 2.5 (t, 1H), 
3.15 (m, 1H), 4.6 (d, 2H), 7.6 (s, 2H), 7.8 (s, 1H). 
Example 11 
Preparation of 
2-(2.6-dichloro-4-pyridyl)-5,6-diethyl-3-propargyl-4(3H)-pyrimidinone 
To a stirred solution of 0.46 g (1.0 mmol) of 
2-(2,6-dichloro-4-pyridyl)-5-ethyl-3-propargyl-6-trifluoromethanesulfonylo 
xy-4(3H)-pyrimidinone, 0.06 g (0.07 mmol) of 
dichloro1,1-bis(diphenylphosphino)ferrocene!palladium(II) dichloromethane 
complex and 0.43 g (2.0 mmol) of K.sub.3 PO.sub.4 in 5 mL of DMF was added 
1.1 mL of 1.0M triethylborane in THF (1.1 mmol). The mixture was stirred 
at room temperature for 22 h and treated with 1 mL of 1:1 12.5% aqueous 
NaOH:30% H.sub.2 O.sub.2. Gas evolution occurred. The mixture was diluted 
with 150 mL of ethyl acetate, washed with 50 mL of water and 50 mL of 
brine, and dried over MgSO.sub.4. Removal of the solvent under reduced 
pressure afforded 0.55 g of a dark oil. This material was purified by 
flash chromatography on a column of 20 g of silica gel which was eluted 
with 50 mL portions of 0, 20, 40, 60, 80 and 100% ether in hexanes. 
Fractions of 15 mL were collected. Fractions 8-10 were combined and 
concentrated to afford 0.05 g of a white solid. Comparison of the .sup.1 H 
NMR and mass spectra of this material with those of an authentic sample 
demonstrated the presence of 
2-(2,6-dichloro-4-pyridyl)-5,6-diethyl-3-propargyl-4(3H)-pyrimidinone. 
Example 12 
Preparation of 
2-(2.6-dichloro-4-pyridyl)-5-methoxy-6-methyl-3-=propargyl-4(3H)-pyrimidin 
one 
A stirred suspension of 0.126 g (1.41 mmol) of copper(I) cyanide in 6 mL of 
dry THF, under a nitrogen atmosphere, was cooled to -70.degree. C. and 2.1 
mL (2.94 mmol) of 1.4M methyllithium in ether was added dropwise over 1h. 
The mixture was stirred at -70.degree. C. for 15 minutes, allowed to warm 
to -50.degree. C. and recooled to -70.degree. C. The cuprate solution was 
added via a canula under nitrogen pressure to a stirred solution of 300 mg 
(0.65 mmol) of 
2-(2,6-dichloro-4-pyridyl)-5-methoxy-3-propargyl-6-trifluoromethanesulfony 
loxy-4(3H)-pyrimidinone in 5 mL of dry THF at -70.degree. C. The reaction 
mixture was stirred for 0.5h at -70.degree. C. and quenched by pouring 
into a solution of 20 mL of 9:1 saturated aqueous NH.sub.4 Cl: 
concentrated aqueous NH.sub.4 OH. The organic layer was separated and the 
THF was removed in vacuo. Ethyl acetate was added to the residue and the 
solution was combined with the aqueous layer. NH.sub.4 OH was added to the 
mixture and the layers were separated. The organic layer was washed once 
with NH.sub.4 OH. The aqueous layers were combined and washed once with 
ethyl acetate. The organic layers were combined, dried over MgSO.sub.4 and 
concentrated to yield 0.17 g of oily product containing approximately a 
3:2 mixture of 
2-(2,6-dichloro-4-pyridyl)-5-methoxy-6-methyl-3-propargyl-4(3H)-pyrimidino 
ne and 2-(2,6-dichloro-4-pyridyl)-5-methoxy-3-propargyl-4(3H)-pyrimidinone. 
The former compound gave .sup.1 H NMR (CDCl.sub.3) .delta. 2.35 (s, 3H), 
2.52 (t, 1H), 3.9 (s, 3H), 4.65 (d, 2H), 7.64 (s, 2H). 
Example 13 
Preparation of 
5-ethyl-2-phenyl-3-(3-trimethylsilyl)propargyl-6-vinyl-4(3H)-pyrimidinone 
To a stirred mixture of 
5-ethyl-2-phenyl-6-trifluoromethanesulfonyloxy-3-(3-trimethylsilyl)proparg 
yl-4(3H)-pyrimidinone (0.800 g, 1.744 mmol), 
tetrakis(triphenylphosphine)palladium(0) (0.040 g, 0.032 mmol, 0.02 equiv) 
and lithium chloride (0.222 g, 5.232 mmol, 3 equiv) in 12 mL of dioxane 
was added vinyltributyltin (0.71 mL, 2.442 mmol, 1.4 equiv) at room 
temperature. The reaction mixture was then heated up to .about.110.degree. 
C. and stirred for 30 minutes. The mixture was cooled to room temperature 
and diluted with 20 mL of water and 50 mL of ethyl acetate. The organic 
layer was separated, and the aqueous layer was extracted with 30 mL of 
ethyl acetate. The combined organic extracts were washed with 30 mL of 
saturated sodium chloride, dried (MgSO.sub.4), filtered, and concentrated. 
The crude product was purified by flash chromatography (silica gel, ethyl 
acetate/hexane, 1/9) to afford 0.48 g (82%) of 
5-ethyl-2-phenyl-3-(3-trimethylsilyl)propargyl-6-vinyl-4(3H)-pyrimidinone: 
mp 91.degree.-3.degree. C.: IR (KBr) 2964, 2168, 1661, 1563, 1520, 1400, 
1246, 1027 cm.sup.-1 .sup.1 H NMR (270 MHz, CDCl3) .delta. 0.17 (s, 9H) 
1.19 (t,J=7.3 Hz, 3H), 2.73 (q, J=14.8 Hz, 2H), 4.62 (s, 2H), 5.61 (dd, 
J.sub.1 =2.0 Hz, J.sub.2 =2=10.6 Hz, 1H), 6.48 (dd, J.sub.1 =2.0 Hz, 
J.sub.2 =16.8 Hz, 1H), 6.91 (dd, J.sub.1 =10.6 Hz, J.sub.2 =16.8 Hz, 1H), 
7.48-7.74 (m, 5H), .sup.13 C NMR (68 MHz, CDCl3) .delta.-0.2, 13.5, 18.6, 
37.2, 89.4, 100.2, 123.2, 128.4, 128.5, 130.2, 131.2, 134.9, 152.2, 156.3, 
162.5. 
Example 14 
Preparation of 5-ethyl-2-phenyl-3-propargyl-6-vinyl-4(3H)-pyrimidinone 
To a stirred solution of 
5-ethyl-2-phenyl-3-(3-trimethylsilyl)propargyl-6-vinyl-4(3H)-pyrimidinone 
(0.35 g, 1.04 mmol) in 10 mL of MeOH was added 1mL of acetic acid followed 
by potassium fluoride (0.302 g, 5.20 mmol, 5 equiv) at room temperature. 
The reaction mixture was stirred for 4.5 hours. The solvent was removed, 
and the residue was dissolved in 50 mL of ethyl acetate and 20 mL of 
water. The organic layer was separated, and the aqueous layer was 
extracted with 30 mL of ethyl acetate. The combined organic extracts were 
washed with 30 mL of saturated sodium chloride, dried (MgSO.sub.4) 
filtered, and concentrated. The crude product was purified by flash 
chromatography (silica gel, ethyl acetate/hexane, 1/9) to afford 0.254 g 
(92%) of 5-ethyl-2-phenyl-3-propargyl-6-vinyl-4(3H)-pyrimidinone: mp 
113.degree.-5.degree. C.; IR (KBr) 3189, 2959, 2105, 1645, 1562, 1530, 
1409, 1180 cm.sup.-1 ; .sup.1 H NMR (270 MHz, CDCl3) .delta. 1.01 (t, 
J=7.3 Hz, 3H), 2.16 (t, J=1.3 Hz, 1H), 2.37 (q, J=14.8 Hz, 2H), 4.41 (d, 
J=1.3 Hz, 2H), 5.44 (dd, J.sub.1 =2.0 Hz, J.sub.2 =10.5 Hz, 1H), 6.30(dd, 
J.sub.1 =2.0 Hz, J.sub.2 =16.8 Hz, 1H), 6.73 (dd, J.sub.1 =10.5 Hz, 
J.sub.2 =16.8 Hz, 1H), 7.33-7.57 (m, 5H); .sup.13 C NMR (68 MHz, 
CDCl.sub.3) .delta. 13.5, 18.6, 36.8, 72.8, 78.6, 123.4, 124.2, 128.5, 
128.8, 130.5, 131.2, 134.8, 152.4, 156.2, 162.7. 
Example 15 
Preparation of 
5-ethyl-2-phenyl-6-(2-trimethylsilyl)ethynyl-3-(3-trimethylsilyl)propargyl 
-4(3H)-pyrimidinone To a stirred mixture of 
5-ethyl-2-phenyl-6-trifluoromethanesulfonyloxy-3-(3-trimethylsily)propargy 
l-4(3H)-pyrimidinone (0.800 g, 1.744 mmol), 
bis(triphenylphosphine)palladium(ll) chloride (0.024 g, 0.032 mmol, 0.02 
equiv) and triethylamine (0.48 mL, 3.488 mmol, 2 equiv) in 16 mL of DMF 
was added (trimethylsilyl)acetylene (0.4 mL, 2.616 mmol, 1.5 equiv) at 
room temperature. The reaction mixture was then heated up to 
.about.65.degree. C and stirred for 3 hours. The mixture was cooled to 
room temperature and the solvent was removed under vacuum. The residue was 
dissolved in 50 mL of ethyl acetate and 20 mL of water. The organic layer 
was separated, and the aqueous layer was extracted with 30 mL of ethyl 
acetate. The combined organic extracts were successively washed with 
2.times.30 mL of water, 30 mL of saturated sodium chloride, dried 
(MgSO.sub.4), filtered, and concentrated. The crude product was purified 
by flash chromatography (silica gel, ethyl acetate/hexane, 1/9) to afford 
0.67 g (95%) of compound 
5-ethyl-2-phenyl-6-(2-trimethylsilyl)ethynyl-3-(3-trimethylsilyl)propargyl 
-4(3H)-pyrimidinone: mp 97.degree.-8.degree. C.; IR (KBr) 2958, 2177, 1669, 
1530, 1409, 1240 cm.sup.-1 ; .sup.1 H NMR (270 MHz, CDCl.sub.3) .delta. 
0.15 (s, 9H), 0.25 (s, 9H), 1.23 (t, J=7.6 Hz, 3H), 2.78 (q, J=14.8 Hz, 
2H), 4.59 (s, 2H), 7.46-7.66 (m, 5H); .sup.13 C NMR (68 MHz, CDCl.sub.3) 
.delta.-0.4, -0.3, 12.2, 21.5, 37.1, 89.8, 99.6, 100.5, 103.2, 128.2, 
128.6, 130.4, 131.7, 134.2, 141.7, 157.9, 161.0. Anal. Calcd for C.sub.23 
H.sub.30 N.sub.2 OSi.sub.2 : C, 67.93;H, 7.44;N, 6.89. Found: C, 68.10: H, 
7.34;N, 9.93. 
Example 16 
Preparation of 5-ethyl-6-ethynyl-2-phenyl-3-propargyl-4(3H)-pyrimidinone 
To a stirred solution of 
5-ethyl-2-phenyl-6-(2-trimethylsilyl)ethynyl-3-(3-trimethylsilyl)propargyl 
-4(3H)-pyrimidinone (0.400 g, 0.984 mmol) in 10 mL of MeOH was added 1 mL 
of acetic acid followed by potassium fluoride (0.572 g, 9.836 mmol, 10 
equiv) at room temperature. The reaction mixture was stirred for 3 hours. 
The solvent was removed, and the residue was dissolved in 50 mL of ethyl 
acetate and 20 mL of water. The organic layer was separated, and the 
aqueous layer was extracted with 30 mL of ethyl acetate. The combined 
organic extracts were washed with 30 mL of saturated sodium chloride, 
dried (MgSO.sub.4), filtered, and concentrated, The crude product was 
purified by flash chromatography (silica gel, ethyl acetate/hexane, 2/8) 
to afford 0.249 g (97%) of 
5-ethyl-6-ethynyl-2-phenyl-3-propargyl-4(3H)-pyrimidinone: mp 
134.degree.-6.degree. C.; IR (KBr) 3254, 3237, 2964, 2105, 1669, 
1566,1524,1409,1179 cm.sup.-1 ; .sup.1 H NMR (270 MHz, CDCl.sub.3) .delta. 
1.06 (t, J=7.3 Hz, 3H), 2.17 (t, J=2.3 Hz, 1H), 2.61 (q, J=14.8 Hz, 2H), 
3.29 (s, 1H), 4.40 (d, J=2.3 Hz, 2H), 7.29-7.51 (m, 5H); .sup.13 C NMR (68 
MHz, CDCl.sub.3) .delta. 12.5,21.3,36.8,73.1, 78.0,79.7,84.6,128.2, 128.8, 
130.6, 132.1, 133.8, 141.2, 157.9, 161.2.