ETHYL 9-BROMONONANOATE

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

Procedure: 1,4,5-Triphenylimidazol-2-one was treated with ethyl 9-bromononanoate and potassium carbonate in butanone, followed by sodium hydroxide in ethanol and water, to give after work-up the title compound, m.p. 123°-124° C., Found:C, 76.9;H, 6.9;N, 5.7%;C30H32N2O3 requires: C, 76.9; H, 6.9; N, 6.0%

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

Procedure: 1,4,5-Triphenylimidazol-2-one was treated with ethyl 9-bromononanoate and potassium carbonate in butanone, followed by sodium hydroxide in ethanol and water, to give after work-up the title compound, m.p. 123°-124° C., Found:C, 76.9;H, 6.9;N, 5.7%;C30H32N2O3 requires: C, 76.9; H, 6.9; N, 6.0%

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a dry reaction tube under nitrogen were charged zinc dust (3.70 g, 56.6 mmol), iodine (479 mg, 1.89 mmol) and dry DMA (20 mL). The mixture was stirred at room temperature until the color of iodine disappeared. Ethyl 9-bromononanoate was added, and the mixture was stirred at 80° C. for 4 hours and then at room temperature overnight. (Completion of the zinc insertion reaction was checked by GCMS analysis of the hydrolyzed reaction mixture.) The reaction mixture was used without further treatment in the subsequent step. GCMS m/z 186 [M]+ (ethyl nonanoate). In a dry reaction tube under nitrogen at room temperature overnight

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

Procedure: A solution of 2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-6(5H)-one ((prepared according to the preparation procedures disclosed in PCT patent application PCT/EP2011/062028, Example 12.1 step 1) (500 mg, 1.518 mmol) and potassium carbonate (1049 mg, 7.59 mmol) in DMF (15 ml) under N2 was treated with ethyl 9-bromononanoate (805 mg, 3.04 mmol) and stirred at RT overnight. A further portion of ethyl 9-bromononanoate (805 mg, 3.04 mmol) was added and stirring continued at RT for 3 days. The mixture was diluted with water and extracted with EtOAc. The combined organic extracts were washed with brine (×3), dried (MgSO4) and the solvent was removed under reduced pressure to afford the titled compound as a yellow oil; according to the preparation procedures stirring continued at RT for 3 days extracted with EtOAc The combined organic extracts were washed with brine (×3) dried (MgSO4) the solvent was removed under reduced pressure

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

Procedure: A solution of 2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-6(5H)-one ((prepared according to the preparation procedures disclosed in PCT patent application PCT/EP2011/062028, Example 12.1 step 1) (500 mg, 1.518 mmol) and potassium carbonate (1049 mg, 7.59 mmol) in DMF (15 ml) under N2 was treated with ethyl 9-bromononanoate (805 mg, 3.04 mmol) and stirred at RT overnight. A further portion of ethyl 9-bromononanoate (805 mg, 3.04 mmol) was added and stirring continued at RT for 3 days. The mixture was diluted with water and extracted with EtOAc. The combined organic extracts were washed with brine (×3), dried (MgSO4) and the solvent was removed under reduced pressure to afford the titled compound as a yellow oil; according to the preparation procedures stirring continued at RT for 3 days extracted with EtOAc The combined organic extracts were washed with brine (×3) dried (MgSO4) the solvent was removed under reduced pressure

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

Procedure: 1,4,5-Triphenylimidazol-2-one was treated with ethyl 9-bromononanoate and potassium carbonate in butanone, followed by sodium hydroxide in ethanol and water, to give after work-up the title compound, m.p. 123°-124° C., Found:C, 76.9;H, 6.9;N, 5.7%;C30H32N2O3 requires: C, 76.9; H, 6.9; N, 6.0%

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

Procedure: The title compound was prepared from ethyl 9-bromononanoate and 4-(3,5-dichloropyridin-4-ylamino)-8-hydroxy-7-methoxy-2H-chromen-2-one (Example 29) following the procedures outlined in Examples 25 & 42. 1H NMR (400 MHz, DMSO-d6): δ 9.50 (s, 1H), 8.81 (s, 2H), 7.93 (d, 1H), 7.19 (d, 1H), 4.63 (s, 1H), 3.97 (t, 2H), 3.91 (s, 3H), 2.17 (t, 2H), 1.66 (m, 2H), 1.52-1.38 (m, 4H), 1.34-1.22 (m, 6H); MS (ESI): 508.9.

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

Procedure: The title compound was prepared from ethyl 9-bromononanoate and 4-(3,5-dichloropyridin-4-ylamino)-8-hydroxy-7-methoxy-2H-chromen-2-one (Example 29) following the procedures outlined in Examples 25 & 42. 1H NMR (400 MHz, DMSO-d6): δ 9.50 (s, 1H), 8.81 (s, 2H), 7.93 (d, 1H), 7.19 (d, 1H), 4.63 (s, 1H), 3.97 (t, 2H), 3.91 (s, 3H), 2.17 (t, 2H), 1.66 (m, 2H), 1.52-1.38 (m, 4H), 1.34-1.22 (m, 6H); MS (ESI): 508.9.

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a dry reaction tube under nitrogen were charged zinc dust (3.70 g, 56.6 mmol), iodine (479 mg, 1.89 mmol) and dry DMA (20 mL). The mixture was stirred at room temperature until the color of iodine disappeared. Ethyl 9-bromononanoate was added, and the mixture was stirred at 80° C. for 4 hours and then at room temperature overnight. (Completion of the zinc insertion reaction was checked by GCMS analysis of the hydrolyzed reaction mixture.) The reaction mixture was used without further treatment in the subsequent step. GCMS m/z 186 [M]+ (ethyl nonanoate). In a dry reaction tube under nitrogen at room temperature overnight

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

Procedure: A solution of 2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-6(5H)-one ((prepared according to the preparation procedures disclosed in PCT patent application PCT/EP2011/062028, Example 12.1 step 1) (500 mg, 1.518 mmol) and potassium carbonate (1049 mg, 7.59 mmol) in DMF (15 ml) under N2 was treated with ethyl 9-bromononanoate (805 mg, 3.04 mmol) and stirred at RT overnight. A further portion of ethyl 9-bromononanoate (805 mg, 3.04 mmol) was added and stirring continued at RT for 3 days. The mixture was diluted with water and extracted with EtOAc. The combined organic extracts were washed with brine (×3), dried (MgSO4) and the solvent was removed under reduced pressure to afford the titled compound as a yellow oil; according to the preparation procedures stirring continued at RT for 3 days extracted with EtOAc The combined organic extracts were washed with brine (×3) dried (MgSO4) the solvent was removed under reduced pressure

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

Procedure: 1,4,5-Triphenylimidazol-2-one was treated with ethyl 9-bromononanoate and potassium carbonate in butanone, followed by sodium hydroxide in ethanol and water, to give after work-up the title compound, m.p. 123°-124° C., Found:C, 76.9;H, 6.9;N, 5.7%;C30H32N2O3 requires: C, 76.9; H, 6.9; N, 6.0%

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

Procedure: The title compound was prepared from ethyl 9-bromononanoate and 4-(3,5-dichloropyridin-4-ylamino)-8-hydroxy-7-methoxy-2H-chromen-2-one (Example 29) following the procedures outlined in Examples 25 & 42. 1H NMR (400 MHz, DMSO-d6): δ 9.50 (s, 1H), 8.81 (s, 2H), 7.93 (d, 1H), 7.19 (d, 1H), 4.63 (s, 1H), 3.97 (t, 2H), 3.91 (s, 3H), 2.17 (t, 2H), 1.66 (m, 2H), 1.52-1.38 (m, 4H), 1.34-1.22 (m, 6H); MS (ESI): 508.9.