1-(2,2-difluoroethyl)piperazine

Conditions: temp:0.00; pressure:0.00; stir:

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 1-(2,2-difluoroethyl)piperazine to afford an off-white powder. HPLC (Condition 4) tR=4.72 min, UPLC-MS (Condition 3) tR=1.05 min, m/z=513 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.57 (br. s, 4H) 2.73 (td, J=15.64, 3.91 Hz, 2H) 3.09-3.22 (m, 4H) 6.13 (s, 1H) 6.67 (br. s, 1H) 7.33 (d, J=8.60 Hz, 2H) 7.86 (d, J=8.99 Hz, 3H) 8.33 (br. s, 1H) 8.73 (s, 1H) 10.40 (br. s, 1H) 12.98-13.22 (m, 1H). to afford an off-white powder

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-[4-(2,2-difluoro-ethyl)-piperazin-1-yl]-thiazol-4-one was prepared from 5-[1-(4-chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-ethylsulfanyl-thiazol-4-one and 1-(2,2-difluoro-ethyl)piperazine following General Procedure C.

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

Procedure: 5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-[4-(2,2-difluoro-ethyl)-piperazin-1-yl]-thiazol-4-one was prepared from 5-[1-(4-chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-ethylsulfanyl-thiazol-4-one and 1-(2,2-difluoro-ethyl)piperazine following General Procedure C.

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

Procedure: 5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-[4-(2,2-difluoro-ethyl)-piperazin-1-yl]-thiazol-4-one was prepared from 5-[1-(4-chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-ethylsulfanyl-thiazol-4-one and 1-(2,2-difluoro-ethyl)piperazine following General Procedure C.

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 1-(2,2-difluoroethyl)piperazine to afford an off-white powder. HPLC (Condition 4) tR=4.72 min, UPLC-MS (Condition 3) tR=1.05 min, m/z=513 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.57 (br. s, 4H) 2.73 (td, J=15.64, 3.91 Hz, 2H) 3.09-3.22 (m, 4H) 6.13 (s, 1H) 6.67 (br. s, 1H) 7.33 (d, J=8.60 Hz, 2H) 7.86 (d, J=8.99 Hz, 3H) 8.33 (br. s, 1H) 8.73 (s, 1H) 10.40 (br. s, 1H) 12.98-13.22 (m, 1H). to afford an off-white powder