(2S,5R)-2,5-dimethylpyrrolidine

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A (1:3) mixture of 1-[4-(3-bromo-propoxy)-phenyl]-cyclohexanecarbonitrile and 1-[4-(3-chloro-propoxy)-phenyl]-cyclohexanecarbonitrile (150 mg, 0.54 mmol), N,N-diisopropylethylamine (187 μL, 1.07 mmol) and (2R,5S)-2,5-dimethylpyrrolidine (145 mg, 1.07 mmol) in NMP (0.5 mL) was heated at 160° C. in the microwave (Smith Personal Synthesiser) for 400 seconds then 170° C. for 600 seconds. The reaction mixture was quenched with NaHCO3 (15 mL) and extracted with ethyl acetate (2×15 mL), dried over Na2SO4, filtered and concentrated in vacuo. The compound was purified by column chromatography on Biotage® silica gel, eluting with dichloromethane:methanol:ammonia, 97:3:0.3 to 90:10:1. Yield=28% 1H NMR (400 MHz, CDCl3) δ7.36 (d, 2H), 6.92 (d, 2H), 4.10-4.04 (m, 2H), 4.00 (t, 2H), 3.88 (dt, 2H), 2.72 (t, 2H), 2.64-2.52 (m, 2H), 2.14-1.98 (m, 4H), 1.94 (pentet, 2H), 1.86-1.78 (m, 2H), 1.42-1.28 (m, 2H), 1.10 (d, 6H); HRMS (ESI+) 343.2380 (M+H)+. The reaction mixture was quenched with NaHCO3 (15 mL) extracted with ethyl acetate (2×15 mL) dried over Na2SO4 filtered concentrated in vacuo The compound was purified by column chromatography on Biotage® silica gel eluting with dichloromethane

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A (1:3) mixture of 1-[4-(3-bromo-propoxy)-phenyl]-cyclohexanecarbonitrile and 1-[4-(3-chloro-propoxy)-phenyl]-cyclohexanecarbonitrile (150 mg, 0.54 mmol), N,N-diisopropylethylamine (187 μL, 1.07 mmol) and (2R,5S)-2,5-dimethylpyrrolidine (145 mg, 1.07 mmol) in NMP (0.5 mL) was heated at 160° C. in the microwave (Smith Personal Synthesiser) for 400 seconds then 170° C. for 600 seconds. The reaction mixture was quenched with NaHCO3 (15 mL) and extracted with ethyl acetate (2×15 mL), dried over Na2SO4, filtered and concentrated in vacuo. The compound was purified by column chromatography on Biotage® silica gel, eluting with dichloromethane:methanol:ammonia, 97:3:0.3 to 90:10:1. Yield=28% 1H NMR (400 MHz, CDCl3) δ7.36 (d, 2H), 6.92 (d, 2H), 4.10-4.04 (m, 2H), 4.00 (t, 2H), 3.88 (dt, 2H), 2.72 (t, 2H), 2.64-2.52 (m, 2H), 2.14-1.98 (m, 4H), 1.94 (pentet, 2H), 1.86-1.78 (m, 2H), 1.42-1.28 (m, 2H), 1.10 (d, 6H); HRMS (ESI+) 343.2380 (M+H)+. The reaction mixture was quenched with NaHCO3 (15 mL) extracted with ethyl acetate (2×15 mL) dried over Na2SO4 filtered concentrated in vacuo The compound was purified by column chromatography on Biotage® silica gel eluting with dichloromethane

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A (1:3) mixture of 1-[4-(3-bromo-propoxy)-phenyl]-cyclohexanecarbonitrile and 1-[4-(3-chloro-propoxy)-phenyl]-cyclohexanecarbonitrile (150 mg, 0.54 mmol), N,N-diisopropylethylamine (187 μL, 1.07 mmol) and (2R,5S)-2,5-dimethylpyrrolidine (145 mg, 1.07 mmol) in NMP (0.5 mL) was heated at 160° C. in the microwave (Smith Personal Synthesiser) for 400 seconds then 170° C. for 600 seconds. The reaction mixture was quenched with NaHCO3 (15 mL) and extracted with ethyl acetate (2×15 mL), dried over Na2SO4, filtered and concentrated in vacuo. The compound was purified by column chromatography on Biotage® silica gel, eluting with dichloromethane:methanol:ammonia, 97:3:0.3 to 90:10:1. Yield=28% 1H NMR (400 MHz, CDCl3) δ7.36 (d, 2H), 6.92 (d, 2H), 4.10-4.04 (m, 2H), 4.00 (t, 2H), 3.88 (dt, 2H), 2.72 (t, 2H), 2.64-2.52 (m, 2H), 2.14-1.98 (m, 4H), 1.94 (pentet, 2H), 1.86-1.78 (m, 2H), 1.42-1.28 (m, 2H), 1.10 (d, 6H); HRMS (ESI+) 343.2380 (M+H)+. The reaction mixture was quenched with NaHCO3 (15 mL) extracted with ethyl acetate (2×15 mL) dried over Na2SO4 filtered concentrated in vacuo The compound was purified by column chromatography on Biotage® silica gel eluting with dichloromethane

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

Procedure: Prepared in a similar manner to the compound of Example 33, from the compound of Example 30 and cis 2,5-dimethylpyrrolidine. δH (DMSO-d6), 9.75 (1H, s), 9.45 (1H, s), 8.56 (1H, d, J 5.6 Hz), 7.84 (2H, m), 7.65 (1H, d, J 9.1 Hz), 7.55 (1H, d, J 5.6 Hz), 7.23 (2H, d, J 8.5 Hz), 6.96 (1H, s), 5.13 (1H, m), 4.22-4.13 (4H, m), 3.22 (1H, dd, J 13.9, 4.6 Hz), 3.04 (1H, dd, J 13.8, 10.6 (Hz), 2.43 (3H, s), 2.12-2.05 (2H, m), 1.70-1.64 (2H, m), 1.24-1.15 (9H, m); m/z (ES+, 70V) 528 (MH+).

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A (1:3) mixture of 1-[4-(3-bromo-propoxy)-phenyl]-cyclohexanecarbonitrile and 1-[4-(3-chloro-propoxy)-phenyl]-cyclohexanecarbonitrile (150 mg, 0.54 mmol), N,N-diisopropylethylamine (187 μL, 1.07 mmol) and (2R,5S)-2,5-dimethylpyrrolidine (145 mg, 1.07 mmol) in NMP (0.5 mL) was heated at 160° C. in the microwave (Smith Personal Synthesiser) for 400 seconds then 170° C. for 600 seconds. The reaction mixture was quenched with NaHCO3 (15 mL) and extracted with ethyl acetate (2×15 mL), dried over Na2SO4, filtered and concentrated in vacuo. The compound was purified by column chromatography on Biotage® silica gel, eluting with dichloromethane:methanol:ammonia, 97:3:0.3 to 90:10:1. Yield=28% 1H NMR (400 MHz, CDCl3) δ7.36 (d, 2H), 6.92 (d, 2H), 4.10-4.04 (m, 2H), 4.00 (t, 2H), 3.88 (dt, 2H), 2.72 (t, 2H), 2.64-2.52 (m, 2H), 2.14-1.98 (m, 4H), 1.94 (pentet, 2H), 1.86-1.78 (m, 2H), 1.42-1.28 (m, 2H), 1.10 (d, 6H); HRMS (ESI+) 343.2380 (M+H)+. The reaction mixture was quenched with NaHCO3 (15 mL) extracted with ethyl acetate (2×15 mL) dried over Na2SO4 filtered concentrated in vacuo The compound was purified by column chromatography on Biotage® silica gel eluting with dichloromethane