| abstract |
The invention is a process for making thrombin inhibitor <EMI ID=1.1 HE=22 WI=66 LX=1013 LY=237 TI=CF> compounds of formula which comprises<BR> <SL COMPACT=COMPACT> <LI>```a) reacting <EMI ID=1.2 HE=11 WI=44 LX=1118 LY=555 TI=CF> with R<SP>3</SP>CN ad R<SP>2</SP>CH<SB>2</SB>CHO in a base selected from a trialkylamine and a metal alkoxide to form <EMI ID=1.3 HE=17 WI=51 LX=1094 LY=823 TI=CF> wherein<BR> ```R<SP>1</SP> is C<SB>1</SB>-C<SB>6</SB> alkyl or benzyl;<BR> ```R<SP>2</SP> is hydrogen,<BR> ```aryl, or<BR> ```C<SB>1</SB>-C<SB>6</SB> alkyl;<BR> HX is selected from hydrochloric acid, sulfuric acid, methanesulfonic acid, phosphoric acid, acetic acid, oxalic acid and hydrogen bromide;<BR> R<SP>3</SP> is potassium, sodium, lithium or trimethylsilyl;<BR> <LI>```b) cyclizing <U>II</U> with oxalyl chloride to form <EMI ID=1.4 HE=126 WI=73 LX=999 LY=1527 TI=CF> <LI>c) aminating <U>III</U> with phenethylamine to produce <LI>d) saponifying and hydrogenating <U>IV</U> to produce <LI>e) coupling <U>V</U> to </SL> to form |