Processes and intermediates for carbamoylpyridone hiv integrase inhibitors

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

• wherein
• R is —CHO, or —CH(OH)(OR4);
• P1 is H or a hydroxyl protecting group;
• P3 is H or a carboxy protecting group;
• R3 is H, halogen, hydroxy, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted lower alkenyl, optionally substituted lower alkoxy, optionally substituted lower alkenyloxy, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heterocyclic group, optionally substituted heterocycleoxy or optionally substituted amino;
• R4 is lower alkyl;
• Rx is H, halo or R2—X—NR1—C(O)—;
• R2 is optionally substituted aryl;
• X is a single bond, a heteroatom group selected from O, S, SO, SO2 , and NH or lower alkylene or lower alkenylene wherein each may be intervened by the heteroatom;
• and
• R1 is H or lower alkyl,
• which comprises the steps of:
• i) reacting a compound of formula (II):
• with an amine of formula (III) or (IV):
• wherein R5 and R6 are independently lower alkyl or R5 and R6 can be alkyl and joined to form a 5-, 6-, or 7-membered ring,
• to produce an intermediate of formula (V) or (VI), respectively:
• and
• ii) refunctionalizing (V) or (VI) to produce (I).

A process for preparing a compound of formula (I):

• wherein
• R is —CH(OH)(OR4);
• P1 is a hydroxyl protecting group;
• P3 is H;
• R3 is H;
• R4 is lower alkyl;
• Rx is R2—X—NR1—C(O)—;
• R2 is aryl optionally substituted with one or more halogen;
• X is lower alkylene;
• and
• R1 is H;
• comprising the steps of:
• i) reacting a compound of formula (II):
• with an amine of formula (III):
• wherein R5 and R6 are independently lower alkyl,
• to produce an intermediate of formula (V)
• and
• ii) refunctionalizing (V) to produce (I).