Efficient method for the conversion of nitriles to amidines

A process for the formation of a compound of the formula (I):

• ##STR25## or a pharmaceutically acceptable salt form thereof;
• wherein:
• R.sup.1 is selected from H or NHR.sup.1a ;
• R.sup.1a is selected from the group consisting of:
• --C(.dbd.O)--O-R.sup.1b,
• --C(.dbd.O)--R.sup.1b,
• --C(.dbd.O)N(R.sup.1b).sub.2,
• C(.dbd.O)NHSO.sub.2 R.sup.1b,
• --C(.dbd.O)NHC(.dbd.O)R.sup.1b,
• --C(.dbd.O)NHC(.dbd.O)OR.sup.1b,
• --C(.dbd.O)NHSO.sub.2 NHR.sup.1b,
• --C(.dbd.S)--NH--R.sup.1b,
• --NH--C(.dbd.O)--O--R.sup.1b,
• --NH--C(.dbd.O)R.sup.1b,
• --NH--C(.dbd.)--NH--R.sup.1b,
• --SO.sub.2 --O--R.sup.1b,
• --SO.sub.2 --R.sup.1b,
• --SO.sub.2 --N(R.sup.1b).sub.2,
• --SO.sub.2 --NHC(.dbd.O)OR.sup.1b,
• --P(.dbd.S)(OR.sup.1b).sub.2,
• --P(.dbd.O)(OR.sup.1b).sub.2,
• --P(.dbd.S)(R.sup.1b).sub.2,
• --P(.dbd.O)(R.sup.1b).sub.2, and ##STR26## R.sup.1b is selected from the group consisting of:
• C.sub.1 -C.sub.8 alkyl substituted with 0-2 R.sup.1c,
• C.sub.2 -C.sub.8 alkenyl substituted with 0-2 R.sup.1c,
• C.sub.2 -C.sub.8 alkynyl substituted with 0-2 R.sup.1c,
• C.sub.3 -C.sub.8 cycloalkyl substituted with 0-2 R.sup.1c,
• aryl substituted with 0-4 R.sup.1c,
• aryl(C.sub.1 -C.sub.6 alkyl)-substituted with 0-4 R.sup.1c,
• a 5-10 membered heterocyclic ring system having 1-3 heteroatoms selected independently from O, S, and N, said heterocyclic ring being substituted with 0-4 R.sup.1c, and
• C.sub.1 -C.sub.6 alkyl substituted with a 5-10 membered heterocyclic ring system having 1-3 heteroatoms selected independently from O, S, and N, said heterocyclic ring being substituted with 0-4R.sup.1c ;
• R.sup.1c is H, halogen, CF.sub.3, CN, NO.sub.2, C.sub.1 -C.sub.8 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.11 cycloalkyl, C.sub.4 -C.sub.11 cycloalkylalkyl, aryl, aryl(C.sub.1 -C.sub.6 alkyl)-, C.sub.1 -C.sub.6 alkoxy, and C.sub.2 -C.sub.5 alkoxycarbonyl;
• R.sup.2 is selected from H or C.sub.1 -C.sub.10 alkyl;
• R.sup.3 and R.sup.4 are independently selected from the group consisting of H, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, C.sub.3 -C.sub.7 cycloalkyl, and aryl substituted with 0-2 R.sup.3a ;
• R.sup.3a is selected from the group consisting of C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, CF.sub.3, NO.sub.2, and NR.sup.3b R.sup.3c ;
• R.sup.3b and R.sup.3c are each independently selected from the group consisting of H, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.10 alkoxycarbonyl, C.sub.2 -C.sub.10 alkylcarbonyl, C.sub.1 -C.sub.10 alkylsulfonyl, heteroaryl(C.sub.1 -C.sub.4 alkyl)sulfonyl, aryl(C.sub.1 -C.sub.10 alkyl)sulfonyl, arylsulfonyl, aryl, heteroarylcarbonyl, heteroarylsulfonyl, and heteroarylalkylcarbonyl, wherein said aryl and heteroaryl are optionally substituted with 0-3 R.sup.3d ;
• R.sup.3d is selected from the group consisting of C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, CF.sub.3, and NO.sub.2 ;
• R.sup.5 is selected from the group consisting of:
• hydroxy, C.sub.1 -C.sub.10 alkyloxy, C.sub.3 -C.sub.11 cycloalkyloxy,
• C.sub.6 -C.sub.10 aryloxy, C.sub.7 -C.sub.11 arylalkyloxy,
• C.sub.3 -C.sub.10 alkylcarbonyloxyalkyloxy,
• C.sub.3 -C.sub.10 alkoxycarbonyloxyalkyloxy,
• C.sub.3 -C.sub.10 alkoxycarbonylalkyloxy,
• C.sub.5 -C.sub.10 cycloalkylcarbonyloxyalkyloxy,
• C.sub.5 -C.sub.10 cycloalkoxycarbonyloxyalkyloxy,
• C.sub.5 -C.sub.10 cycloalkoxycarbonylalkyloxy,
• C.sub.8 -C.sub.1 l aryloxycarbonylalkyloxy,
• C.sub.8 -C.sub.12 aryloxycarbonyloxyalkyloxy,
• C.sub.8 -C.sub.12 arylcarbonyloxyalkyloxy,
• C.sub.5 -C.sub.10 alkoxyalkylcarbonyloxyalkyloxy,
• 5-(C.sub.5 -C.sub.10 alkyl)-1,3-dioxa-cyclopenten-2-one-yl)-methyloxy,
• (5-aryl-1,3-dioxa-cyclopenten-2-one-yl)-methyloxy, and (R.sup.5a)HN-(C.sub.1 -C.sub.10 alkoxy)-;
• R.sup.5a is selected from the group consisting of H, C.sub.1 -C.sub.4 alkyl, aryl(C.sub.1 -C.sub.10 alkoxy)carbonyl, C.sub.2 -C.sub.10 alkoxycarbonyl, and C.sub.3 -C.sub.6 alkenyl;
• n is 0-4;
• a is a single or double bond, with the proviso that if a is a double bond, it is not simultaneously substituted with R.sup.3 and R.sup.4 ;
• said process comprising:
• contacting a compound of formula (IV):
• ##STR27## wherein:
• R.sup.6 is selected from the group consisting of H, CF.sub.3, CF.sub.2 CF.sub.3, CF.sub.2 CF.sub.2 CF.sub.3, CF.sub.2 CF.sub.2 CF.sub.2 CF.sub.3, C.sub.1 -C.sub.8 alkyl, C.sub.1 -C.sub.8 perfluoroalkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, C.sub.3 -C.sub.11 cycloalkyl, C.sub.4 -C.sub.11 cycloalkylalkyl, aryl(C.sub.1 -C.sub.6 alkyl)-, C.sub.1 -C.sub.6 alkoxy, C.sub.7 -C.sub.10 arylalkyloxy, C.sub.1 -C.sub.6 alkyloxy, aryloxy and aryl substituted with 0-5 R.sup.6c ;
• R.sup.6c is selected from the group consisting of H, halo, CF.sub.3, CN, NO.sub.2, NR.sup.6d R.sup.6e, C.sub.1 -C.sub.8 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.11 cycloalkyl, C.sub.4 -C.sub.11 cycloalkylalkyl, aryl, aryl(C.sub.1 -C.sub.6 alkyl)-, C.sub.1 -C.sub.6 alkoxy, and C.sub.2 -C.sub.5 alkoxycarbonyl;
• R.sup.6d and R.sup.6e are independently selected from the group consisting of H, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.10 alkoxycarbonyl, C.sub.2 -C.sub.10 alkylcarbonyl, C.sub.1 -C.sub.10 alkylsulfonyl, aryl, aryl(C.sub.1 -C.sub.10 alkyl)sulfonyl, arylsulfonyl, heteroaryl(C.sub.1 -C.sub.4 alkyl)sulfonyl, heteroarylcarbonyl, heteroarylsulfonyl, or heteroarylalkylcarbonyl, wherein said aryl and heteroaryl are optionally substituted with 0-3 substituents selected from the group consisting of C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, CF.sub.3, and NO.sub.2 ;
• with hydrogen under a suitable pressure in the presence of a hydrogenation catalyst to form a compound of formula (I) or a pharmaceutically acceptable salt form thereof.