2-(isocyanatomethyl)oxolane

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

Procedure: This compound was prepared by using procedures analogous to those described for the synthesis of Example 30 (Step 6) starting from N-{3-[7-(1-piperidin-4-yl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-3-yl]phenyl}-N′-(2,2,2-trifluoroethyl)urea and 2-(isocyanatomethyl)tetrahydrofuran (Matrix Scientific, Cat. No. 030196). LCMS (M+H)+: m/z=612.3. This compound was prepared those described for the synthesis of Example 30 (Step 6)

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

Procedure: 80 mg (0.23 mmol) of ethyl-N-{5-[4-(trifluoromethyl)phenyl]piperidin-3-yl}benzamide were initially charged in 2 ml of THF, and 29 mg (0.23 mmol) of 2-(isocyanatomethyl)tetrahydrofuran and 35 μl (0.25 mmol) of triethylamine were added. The mixture was stirred at RT overnight. The reaction mixture was then purified by preparative HPLC (Reprosil C18, water/acetonitrile gradient). Yield: 88 mg (81% of theory) The reaction mixture was then purified by preparative HPLC (Reprosil C18, water/acetonitrile gradient)

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

Procedure: This compound was prepared by using procedures analogous to those described for the synthesis of Example 30 (Step 6) starting from N-{3-[7-(1-piperidin-4-yl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-3-yl]phenyl}-N′-(2,2,2-trifluoroethyl)urea and 2-(isocyanatomethyl)tetrahydrofuran (Matrix Scientific, Cat. No. 030196). LCMS (M+H)+: m/z=612.3. This compound was prepared those described for the synthesis of Example 30 (Step 6)

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

Procedure: 80 mg (0.23 mmol) of ethyl-N-{5-[4-(trifluoromethyl)phenyl]piperidin-3-yl}benzamide were initially charged in 2 ml of THF, and 29 mg (0.23 mmol) of 2-(isocyanatomethyl)tetrahydrofuran and 35 μl (0.25 mmol) of triethylamine were added. The mixture was stirred at RT overnight. The reaction mixture was then purified by preparative HPLC (Reprosil C18, water/acetonitrile gradient). Yield: 88 mg (81% of theory) The reaction mixture was then purified by preparative HPLC (Reprosil C18, water/acetonitrile gradient)

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

Procedure: This compound was prepared by using procedures analogous to those described for the synthesis of Example 30 (Step 6) starting from N-{3-[7-(1-piperidin-4-yl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-3-yl]phenyl}-N′-(2,2,2-trifluoroethyl)urea and 2-(isocyanatomethyl)tetrahydrofuran (Matrix Scientific, Cat. No. 030196). LCMS (M+H)+: m/z=612.3. This compound was prepared those described for the synthesis of Example 30 (Step 6)