1-(2-isothiocyanatoethyl)piperidine

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

Procedure: To a solution of 3-(2-Fluoro-4-iodo-phenylamino)-isonicotinic acid hydrazide (300 mg; 0.81 mmol; 1 eq) in DCM (5 mL), 1-(2-Isothiocyanato-ethyl)-piperidine (192 mg; 1.13 mmol; 1.4 eq) was added. The reaction mixture was refluxed for 4 hrs under argon. A yellow solid precipitated out and filtered to afford an intermediated that was suspended in ethanol (5 mL). Iodomethane (148 mg; 1.05 mmol; 1.3 eq) was added to the reaction mixture and stirred overnight at RT, then heated to 80° C. and stirred for another 2 hr. The mixture was filtered to give a yellow solid product 40 mg. LC/MS (Method A) [3.89 min; 509(M+1)] The reaction mixture was refluxed for 4 hrs under argon A yellow solid precipitated out filtered to afford an intermediated heated to 80° C. stirred for another 2 hr The mixture was filtered

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

Procedure: A mixture of 3-phenyl-3-isobutyl-4,5,6,7-tetrahydrofuro[3,4-c]pyridin-1(3H)-one (50 mg, 0.18 mmol) and 1-(isothiocyanatoethyl)piperidine (45.7 mg, 0.28 mmol) in dichloromethane (5 mL) was stirred at room temperature for 1 h. The solvent was removed and the resulting residue was purified on silica to give the desired product (52 mg, 64.0%). 1H NMR (300 Hz, CDCl3) δ 0.87 (t, J=6.0, 3H), 0.96 (t, d=6.0, 3H), 1.40-1.63 (m, 6H), 1.63-1.75 (m, 1H), 1.78-1.90 (m, 1H), 2.30-2.60 (m, 10H), 2.58-2.70 (m, 3H), 3.83-3.95 (m, 1H), 4.26 (d, J=18.0, 1H), 5.17 (d, J=18.0, 1H), 7.02 (br s, 1H), 7.26-7.40 (m, 5H). The solvent was removed the resulting residue was purified on silica

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

Procedure: To a solution of 3-(2-Fluoro-4-iodo-phenylamino)-isonicotinic acid hydrazide (300 mg; 0.81 mmol; 1 eq) in DCM (5 mL), 1-(2-Isothiocyanato-ethyl)-piperidine (192 mg; 1.13 mmol; 1.4 eq) was added. The reaction mixture was refluxed for 4 hrs under argon. A yellow solid precipitated out and filtered to afford an intermediated that was suspended in ethanol (5 mL). Iodomethane (148 mg; 1.05 mmol; 1.3 eq) was added to the reaction mixture and stirred overnight at RT, then heated to 80° C. and stirred for another 2 hr. The mixture was filtered to give a yellow solid product 40 mg. LC/MS (Method A) [3.89 min; 509(M+1)] The reaction mixture was refluxed for 4 hrs under argon A yellow solid precipitated out filtered to afford an intermediated heated to 80° C. stirred for another 2 hr The mixture was filtered