Methods for the preparation of hcv polymerase inhibitors

A method of preparing a compound of formula (Ia):

• wherein:
• R1 is C1-C6 alkyl or C3-C6 cycloalkyl;
• R2a, R2b, and R2c are each independently selected from hydrogen, halogen, C1-C6 alkyl, C3-C6 cycloalkyl, —OR12a, —CF3, —CN, and —NR12aR12b;
• R4 is selected from hydrogen, C1-C6 alkyl, —(CR9R10)nR11, —CF3, halogen, —OR12a, —CN, and —NR12aR12b;
• R5 is selected from hydrogen, C1-C6 alkyl, —(CR9R10)nR11, —CF3, halogen, —OR12a, —CN, and —NR12aR12b;
• R6 is selected from hydrogen, C1-C6 alkyl, —(CR9R10)nR11, —CF3, halogen, —OR12a, —CN, and —NR12aR12b;
• R7 is selected from hydrogen, C1-C6 alkyl, —(CR9R10)nR11, —CF3, halogen, —OR12a, —CN, and —NR12aR12b;
• each R9 and R10 is independently selected from hydrogen and C1-C6 alkyl, or R9 and
• R10, together with the carbon atom to which they are attached, form a C3-C6 cycloalkyl group;
• each R11 is independently selected from hydrogen, C1-C6 alkyl, halogen, —OR12a, —CN, —CF3, and —NR9R10;
• each R12a and R12b is independently selected from hydrogen and C1-C6 alkyl;
• and
• each n is independently chosen and is an integer from 0 to 5;
• said method comprising:
• a) treating a compound of formula (V), wherein R1 is defined above, with an anion of a compound of formula (X), wherein R13 is hydrogen, C1-C6 alkyl, —Si(C1-C6 alkyl)3, or —CH2(C6-C10 aryl), wherein said C6-C10 aryl group is optionally substituted with at least one substituent selected from halogen, C1-C6 alkyl, —OH, —OCH3, and —N(C1-C6 alkyl)2, to afford a compound of formula (IV);
• b) hydrolyzing the compound of formula (IV) to afford a compound of formula (IV) wherein R13 is hydrogen;
• c) treating the compound of formula (IV) with a combination of reagents to afford a compound of formula (III), wherein P1 is hydrogen or a suitable protecting group and R14 is C1-C6 alkyl or —CH2(C6-C10 aryl), wherein said C6-C10 aryl group is optionally substituted with at least one substituent selected from halogen, C1-C6 alkyl, —OH, —OCH3, and —N(C1-C6 alkyl)2;
• d) treating the compound of formula (III) with an acid or base to afford a compound of formula (II), and
• e) treating the compound of formula (II) with a compound of formula (Ixa), to afford the compound of formula (Ia)