(3R,4R)-4-fluoropyrrolidin-3-ol

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

Procedure: The title compound was prepared in an analogous fashion to that described in Example 33 using 6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)nicotinamide (Stage 48.2) and trans-4-fluoropyrrolidin-3-ol to afford an amorphous white powder. HPLC (Condition 4) tR=5.21 min, UPLC-MS (Condition 3) tR=0.99 min, m/z=468.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 3.06 (d, J=12.12 Hz, 1H) 3.33-3.49 (m, 2H) 3.53-3.76 (m, 1H) 4.15 (br. s, 1H) 4.77-5.02 (m, 1H) 5.36-5.50 (m, 1H) 6.41 (br. s, 1H) 7.31 (d, J=8.60 Hz, 2H) 7.79-7.91 (m, 3H) 8.06 (d, J=1.96 Hz, 1H) 8.73 (br. s, 1H) 10.21 (s, 1H) 12.90-13.21 (m, 1H). to afford an amorphous white powder

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

Procedure: The title compound was prepared in an analogous fashion to that described in Example 33 using 6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)nicotinamide (Stage 48.2) and trans-4-fluoropyrrolidin-3-ol to afford an amorphous white powder. HPLC (Condition 4) tR=5.21 min, UPLC-MS (Condition 3) tR=0.99 min, m/z=468.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 3.06 (d, J=12.12 Hz, 1H) 3.33-3.49 (m, 2H) 3.53-3.76 (m, 1H) 4.15 (br. s, 1H) 4.77-5.02 (m, 1H) 5.36-5.50 (m, 1H) 6.41 (br. s, 1H) 7.31 (d, J=8.60 Hz, 2H) 7.79-7.91 (m, 3H) 8.06 (d, J=1.96 Hz, 1H) 8.73 (br. s, 1H) 10.21 (s, 1H) 12.90-13.21 (m, 1H). to afford an amorphous white powder

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

Procedure: The title compound was prepared in an analogous fashion to that described in Example 38 using 6-chloro-5-(1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 38.1) and trans-4-fluoropyrrolidin-3-ol (Stage 74.1). The product was purified by chromatography on Silica gel, preparative TLC (eluent EtOAc), followed by preparative SFC (Column 2-EP, from 17-22% in 6 min) to afford the title product as a white solid. UPLC-MS (Condition 8) tR=0.94 min, m/z=452.1 [M+H]+; 1H-NMR (600 MHz, DMSO-d6) δ ppm 3.07 (d, J=12.42 Hz, 1H) 3.30-3.51 (m, 2H) 3.56-3.74 (m, 1H) 4.17 (br. s, 1H) 4.86-5.00 (m, 1H) 5.42-5.52 (m, 1H) 6.38-6.46 (m, 1H) 7.35 (d, J=8.66 Hz, 2H) 7.53-7.91 (m, 3H) 8.03-8.13 (m, 1H) 8.71-8.82 (m, 1H) 10.24 (s, 1H). The title compound was prepared in an analogous fashion to The product was purified by chromatography on Silica gel, preparative TLC (eluent EtOAc) followed by preparative SFC (Column 2-EP, from 17-22% in 6 min)

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

Procedure: The title compound was prepared in an analogous fashion to that described in Example 33 using 6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)nicotinamide (Stage 48.2) and trans-4-fluoropyrrolidin-3-ol to afford an amorphous white powder. HPLC (Condition 4) tR=5.21 min, UPLC-MS (Condition 3) tR=0.99 min, m/z=468.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 3.06 (d, J=12.12 Hz, 1H) 3.33-3.49 (m, 2H) 3.53-3.76 (m, 1H) 4.15 (br. s, 1H) 4.77-5.02 (m, 1H) 5.36-5.50 (m, 1H) 6.41 (br. s, 1H) 7.31 (d, J=8.60 Hz, 2H) 7.79-7.91 (m, 3H) 8.06 (d, J=1.96 Hz, 1H) 8.73 (br. s, 1H) 10.21 (s, 1H) 12.90-13.21 (m, 1H). to afford an amorphous white powder

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

Procedure: The title compound was prepared in an analogous fashion to that described in Example 38 using 6-chloro-5-(1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 38.1) and trans-4-fluoropyrrolidin-3-ol (Stage 74.1). The product was purified by chromatography on Silica gel, preparative TLC (eluent EtOAc), followed by preparative SFC (Column 2-EP, from 17-22% in 6 min) to afford the title product as a white solid. UPLC-MS (Condition 8) tR=0.94 min, m/z=452.1 [M+H]+; 1H-NMR (600 MHz, DMSO-d6) δ ppm 3.07 (d, J=12.42 Hz, 1H) 3.30-3.51 (m, 2H) 3.56-3.74 (m, 1H) 4.17 (br. s, 1H) 4.86-5.00 (m, 1H) 5.42-5.52 (m, 1H) 6.38-6.46 (m, 1H) 7.35 (d, J=8.66 Hz, 2H) 7.53-7.91 (m, 3H) 8.03-8.13 (m, 1H) 8.71-8.82 (m, 1H) 10.24 (s, 1H). The title compound was prepared in an analogous fashion to The product was purified by chromatography on Silica gel, preparative TLC (eluent EtOAc) followed by preparative SFC (Column 2-EP, from 17-22% in 6 min)