Process for synthesis of a 2-thioalkyl pyrimidine

A method for preparing a compound of Formula 8,

• wherein
• R2 is halogen, or C1-C4 alkyl;
• each R3 is independently halogen, cyano, amino, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkoxy, C2-C4 alkoxycarbonyl, C2-C4 alkylcarbonyloxy, C2-C4 alkoxyalkyl or C1-C4 haloalkyl;
• each R4 is independently halogen, cyano, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy or SCF3;
• m is 0, 1, 2 or 3;
• and
• r is 0, 1 or 2;
• comprising treating a compound of Formula 2
• wherein
• R2 is halogen, or C1-C4 alkyl;
• and
• X is Cl or OH
• in the presence of a halogenating agent and a compound of Formula 3
• wherein
• RA and RB are each independently C1-C4 alkyl;
• or
• RA and RB are taken together to be —(CH2)4—, —(CH2)5— or —CH2CH2OCH2CH2— to provide an intermediate of Formula 4
• wherein
• R2 is halogen, or C1-C4 alkyl;
• and
• RA and RB are each independently C1-C4 alkyl;
• or
• RA and RB are taken together to be —(CH2)4—, —(CH2)5— or —CH2CH2OCH2CH2—;
• treating the intermediate of Formula 4 with an acid salt of a compound of Formula 5
• wherein R1 is C1-C4 alkyl;
• in the presence of a base to prepare a compound of Formula 1
• wherein
• R1 is C1-C4 alkyl;
• R2 is halogen, or C1-C4 alkyl;
• treating the compound of Formula 1 with an oxidant to provide a compound of Formula 6
• wherein
• R1 is C1-C4 alkyl;
• and
• R2 is halogen, or C1-C4 alkyl;
• and
• treating the compound of Formula 6 in the presence of a second base with a compound of
• wherein
• each R3 is independently halogen, cyano, amino, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkoxy, C2-C4 alkoxycarbonyl, C2-C4 alkylcarbonyloxy, C2-C4 alkoxyalkyl or C1-C4 haloalkyl;
• each R4 is independently halogen, cyano, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy or SCF3;
• m is 0, 1, 2 or 3;
• and
• r is 0, 1 or 2.