(4aS,7aS)-2,3,4,4a,5,6,7,7a-octahydropyrrolo[3,4-b][1,4]oxazine

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound is prepared analogously to the procedure of Example 8 by reaction of 6,7-difluoro-1-((1R,2S)-2-fluorocyclopropyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid with (1S,6S)-2-oxa-5,8-diazabicyclo[4.3.0]nonane.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 200 mg (0.63 mmol) of ethyl 8-cyano-1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate are stirred under argon at 40-45° C. for 2 hours with 97 mg (0.75 mmol) of (1S,6S)-2-oxa-5,8-diazabicyclo[4.3.0]nonane and 0.17 ml of triethylamine in 3 ml of acetonitrile. All volatile components are removed in vacuo, the residue is treated with water, insoluble material is filtered off and the filtrate is extracted with dichloromethane. The organic phase is dried over sodium sulphate and then concentrated in vacuo. The resulting residue is dissolved in 6 ml of tetrahydrofuran and 2 ml of water and treated with 30 mg (0.72 mmol) of lithium hydroxide monohydrate. After stirring at room temperature for 16 hours, (he mixture is acidified with dil. hydrochloric acid and the resulting precipitate is filtered off with suction and dried. All volatile components are removed in vacuo the residue is treated with water, insoluble material is filtered off the filtrate is extracted with dichloromethane The organic phase is dried over sodium sulphate concentrated in vacuo The resulting residue is dissolved in 6 ml of tetrahydrofuran the resulting precipitate is filtered off with suction dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound is prepared analogously to the procedure of Example 8 by reaction of 6,7-difluoro-1-((1R,2S)-2-fluorocyclopropyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid with (1S,6S)-2-oxa-5,8-diazabicyclo[4.3.0]nonane.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 200 mg (0.63 mmol) of ethyl 8-cyano-1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate are stirred under argon at 40-45° C. for 2 hours with 97 mg (0.75 mmol) of (1S,6S)-2-oxa-5,8-diazabicyclo[4.3.0]nonane and 0.17 ml of triethylamine in 3 ml of acetonitrile. All volatile components are removed in vacuo, the residue is treated with water, insoluble material is filtered off and the filtrate is extracted with dichloromethane. The organic phase is dried over sodium sulphate and then concentrated in vacuo. The resulting residue is dissolved in 6 ml of tetrahydrofuran and 2 ml of water and treated with 30 mg (0.72 mmol) of lithium hydroxide monohydrate. After stirring at room temperature for 16 hours, (he mixture is acidified with dil. hydrochloric acid and the resulting precipitate is filtered off with suction and dried. All volatile components are removed in vacuo the residue is treated with water, insoluble material is filtered off the filtrate is extracted with dichloromethane The organic phase is dried over sodium sulphate concentrated in vacuo The resulting residue is dissolved in 6 ml of tetrahydrofuran the resulting precipitate is filtered off with suction dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 200 mg (0.63 mmol) of ethyl 8-cyano-1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate are stirred under argon at 40-45° C. for 2 hours with 97 mg (0.75 mmol) of (1S,6S)-2-oxa-5,8-diazabicyclo[4.3.0]nonane and 0.17 ml of triethylamine in 3 ml of acetonitrile. All volatile components are removed in vacuo, the residue is treated with water, insoluble material is filtered off and the filtrate is extracted with dichloromethane. The organic phase is dried over sodium sulphate and then concentrated in vacuo. The resulting residue is dissolved in 6 ml of tetrahydrofuran and 2 ml of water and treated with 30 mg (0.72 mmol) of lithium hydroxide monohydrate. After stirring at room temperature for 16 hours, (he mixture is acidified with dil. hydrochloric acid and the resulting precipitate is filtered off with suction and dried. All volatile components are removed in vacuo the residue is treated with water, insoluble material is filtered off the filtrate is extracted with dichloromethane The organic phase is dried over sodium sulphate concentrated in vacuo The resulting residue is dissolved in 6 ml of tetrahydrofuran the resulting precipitate is filtered off with suction dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound is prepared analogously to the procedure of Example 8 by reaction of 6,7-difluoro-1-((1R,2S)-2-fluorocyclopropyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid with (1S,6S)-2-oxa-5,8-diazabicyclo[4.3.0] nonane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound is prepared analogously to the procedure of Example 8 by reaction of 6,7-difluoro-1-((1R,2S)-2-fluorocyclopropyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid with (1S,6S)-2-oxa-5,8-diazabicyclo[4.3.0] nonane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound is prepared analogously to the procedure of Example 8 by reaction of 6,7-difluoro-1-((1R,2S)-2-fluorocyclopropyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid with (1S,6S)-2-oxa-5,8-diazabicyclo[4.3.0] nonane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 200 mg (0.63 mmol) of ethyl 8-cyano-1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate are stirred under argon at 40-45° C. for 2 hours with 97 mg (0.75 mmol) of (1S,6S)-2-oxa-5,8-diazabicyclo[4.3.0]nonane and 0.17 ml of triethylamine in 3 ml of acetonitrile. All volatile components are removed in vacuo, the residue is treated with water, insoluble material is filtered off and the filtrate is extracted with dichloromethane. The organic phase is dried over sodium sulphate and then concentrated in vacuo. The resulting residue is dissolved in 6 ml of tetrahydrofuran and 2 ml of water and treated with 30 mg (0.72 mmol) of lithium hydroxide monohydrate. After stirring at room temperature for 16 hours, the mixture is acidified with dil. hydrochloric acid and the resulting precipitate is filtered off with suction and dried. All volatile components are removed in vacuo the residue is treated with water, insoluble material is filtered off the filtrate is extracted with dichloromethane The organic phase is dried over sodium sulphate concentrated in vacuo The resulting residue is dissolved in 6 ml of tetrahydrofuran the resulting precipitate is filtered off with suction dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 200 mg (0.63 mmol) of ethyl 8-cyano-1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate are stirred under argon at 40-45° C. for 2 hours with 97 mg (0.75 mmol) of (1S,6S)-2-oxa-5,8-diazabicyclo[4.3.0]nonane and 0.17 ml of triethylamine in 3 ml of acetonitrile. All volatile components are removed in vacuo, the residue is treated with water, insoluble material is filtered off and the filtrate is extracted with dichloromethane. The organic phase is dried over sodium sulphate and then concentrated in vacuo. The resulting residue is dissolved in 6 ml of tetrahydrofuran and 2 ml of water and treated with 30 mg (0.72 mmol) of lithium hydroxide monohydrate. After stirring at room temperature for 16 hours, the mixture is acidified with dil. hydrochloric acid and the resulting precipitate is filtered off with suction and dried. All volatile components are removed in vacuo the residue is treated with water, insoluble material is filtered off the filtrate is extracted with dichloromethane The organic phase is dried over sodium sulphate concentrated in vacuo The resulting residue is dissolved in 6 ml of tetrahydrofuran the resulting precipitate is filtered off with suction dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.00 g (3.26 mmol) of 7-chloro-8-cyano-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid are stirred under argon at 40-45° C. for 25 hours with 501 mg (3.91 mmol) of (1S,6S)-2-oxa-5,8-diazabicyclo[4.3.0]nonane and 0.9 ml of triethylamine in 30 ml of acetonitrile. All volatile components are removed in vacuo and the residue is recrystallized from ethanol. All volatile components are removed in vacuo the residue is recrystallized from ethanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound is prepared analogously to the procedure of Example 8 by reaction of 6,7-difluoro-1-((1R,2S)-2-fluorocyclopropyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid with (1S,6S)-2-oxa-5,8-diazabicyclo[4.3.0]nonane.