Antibacterial cyclopenta[C]pyrrole substituted 3,4-dihydro-1H-[1,8]naphthyridinones

1. A process for preparing a compound of formula (I),

comprising

reacting an intermediate of formula (II) with an intermediate of formula (III),

wherein

A represents —C≡C—or

the bond represents a single bond or a double bond;

X represents carbon or nitrogen, and when X represents nitrogen then the bond represents a single bond;

Z 1 represents CH or N;

R 1 is hydrogen, C 1-4 alkyl or halo;

R 2 is hydrogen, C 1-4 alkyl or halo;

R 3 is hydrogen, C 1-6 alkyl, hydroxy or halo;

R 4 is hydrogen, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkyloxy,

C 1-4 alkyloxycarbonyl, aminocarbonyl, mono- or di(C 1-4 alkyl)-aminocarbonyl, aryl, aryloxy, arylcarbonyl, arylsulfonyl, heteroaryl, C 1-6 alkyl substituted with cyano, C 1-6 alkyl substituted with aryl or aryloxy, or C 1-6 alkyl substituted with heteroaryl;

wherein said heteroaryl is furanyl, thiophenyl, pyrrolyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, triazolyl, tetrazolyl, isothiazolyl, thiadiazolyl, oxadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzo[1,3]dioxolyl, benzofuranyl, benzothiazolyl, indolyl, 2,3-dihydro-1H-indolyl, tetrahydrothiophenyl, or quinolinyl, and wherein each heteroaryl may be substituted with one or two substituents each independently selected from halo, cyano, C 1-4 alkyl, C 1-4 alkyloxy, C 1-4 alkylcarbonyl, and phenyl;

wherein said aryl is phenyl, or phenyl substituted with one, two or three substituents each individually selected from halo, hydroxy, C 1-4 alkyl,

C 1-4 alkyloxy, polyhaloC 1-4 alkyl, polyhaloC 1-4 alkyloxy, cyano, nitro, and amino; and

Y is hydroxy or halo.

2. A process as claimed in claim 1 , wherein Y is hydroxy.

3. A process as claimed in claim 1 , wherein Y is halo.

4. A process as claimed in claim 1 , wherein A is —C(R 2 )═C(R 1 )—.

5. A process as claimed in claim 2 , wherein said reacting is performed in the presence of coupling agents EDCI and hydroxybenzotriazole.

6. A process as claimed in claim 5 , wherein A is —C(R 2 )═C(R 1 )—, Z 1 is CH, R 1 is hydrogen, R 2 is hydrogen, R 3 is hydrogen, R 4 is phenyl, the bond represents a double bond, and X is carbon.

7. A process for preparing a compound of formula (I),

comprising

reacting an intermediate of formula (V) with an intermediate of formula (VI),

wherein

A is

the bond represents a single bond or a double bond;

X represents carbon or nitrogen, and when X represents nitrogen then the bond represents a single bond;

Z l represents CH or N;

R 1 is hydrogen, C 1-4 olkyl or halo;

R 2 is hydrogen, C 1-4 olkyl or halo;

R 3 is hydrogen, C 1-6 alkyl, hydroxy or halo;

R 4 is hydrogen, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkyloxy,

C 1-4 alkyloxycarbonyl, aminocarbonyl, mono- or di(C 1-4 alkyl)-aminocarbonyl, aryl, aryloxy, arylcarbonyl, arylsulfonyl, heteroaryl, C 1-6 alkyl substituted with cyano, C 1-6 alkyl substituted with aryl or aryloxy, or C 1-6 alkyl substituted with heteroaryl;

wherein said heteroaryl is furanyl, thiophenyl, pyrrolyl, pyrazolyl, imidazolyl, isoxazolyl, thiazolyl, triazolyl, tetrazolyl, isothiazolyl, thiadiazolyl, oxadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzo[1,3]dioxolyl, benzofuranyl, benzothiazolyl, indolyl, 2,3-dihydro-1H-indolyl, tetrahydrothiophenyl, or quinolinyl, and wherein each heteroaryl may be substituted with one or two substituents each independently selected from halo, cyano, C 1-4 alkyl, C 1-4 alkyloxy, C 1-4 alkylcarbonyl, and phenyl;

wherein said aryl is phenyl, or phenyl substituted with one, two or three substituents each individually selected from halo, hydroxy, C 1-4 alkyl,

C 1-4 alkyloxy, polyhaloC 1-4 alkyl, polyhaloC 1-4 alkyloxy, cyano, nitro, and amino;

Y is hydroxy or halo; and

X a1 represents a suitable leaving group.

8. A process as claimed in claim 7 , wherein X a1 is halo.

9. A process as claimed in claim 8 , wherein X a1 is bromo.

10. A process as claimed in claim 7 , wherein said reacting is performed under metal catalyst coupling reaction conditions.

11. A process as claimed in claim 10 , wherein said metal catalyst coupling reaction conditions are Heck reaction conditions.

12. A process as claimed in claim 11 , wherein said Heck reaction conditions include using a palladium-based catalyst.

13. A process as claimed in claim 12 , wherein said palladium-based catalyst is palladium acetate.