triethyloxidanium;hexafluorophosphate

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

Procedure: To a solution of (S)-2-(tert-butoxycarbonyl(methyl)amino)-6-methoxy-6-oxohexyl 1H-imidazole-1-carboxylate (2 g, 5.4 mmol) in DCM (10 mL) was added a solution of triethyloxonium hexafluorophosphate (1.61 g, 6.5 mmol, 1.2 equiv.) in DCM (5 mL) dropwise at 0° C. The solution was warmed up to RT and stirred for 15 min. A solution of isoquinolin-3-amine (0.94 g, 6.5 mmol, 1.2 equiv.) in DCM (5 mL) was added. The solution was stirred for overnight. DCM was removed and the residue was purified on RP-HPLC using a mixture of acetonitrile and H2O to give (S)-methyl 5-(tert-butoxycarbonyl(methyl)amino)-6-(isoquinolin-3-ylcarbamoyloxy)hexanoate (1.4 g, 58%). LRMS (M+H+) m/z 446.2. The solution was stirred for overnight DCM was removed the residue was purified on RP-HPLC a mixture of acetonitrile and H2O

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

Procedure: To a solution of (S)-2-(tert-butoxycarbonyl(methyl)amino)-6-methoxy-6-oxohexyl 1H-imidazole-1-carboxylate (2 g, 5.4 mmol) in DCM (10 mL) was added a solution of triethyloxonium hexafluorophosphate (1.61 g, 6.5 mmol, 1.2 equiv.) in DCM (5 mL) dropwise at 0° C. The solution was warmed up to RT and stirred for 15 min. A solution of isoquinolin-3-amine (0.94 g, 6.5 mmol, 1.2 equiv.) in DCM (5 mL) was added. The solution was stirred for overnight. DCM was removed and the residue was purified on RP-HPLC using a mixture of acetonitrile and H2O to give (S)-methyl 5-(tert-butoxycarbonyl(methyl)amino)-6-(isoquinolin-3-ylcarbamoyloxy)hexanoate (1.4 g, 58%). LRMS (M+H+) m/z 446.2. The solution was stirred for overnight DCM was removed the residue was purified on RP-HPLC a mixture of acetonitrile and H2O

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

Procedure: (2S)-1-[(4-Fluorophenyl)sulfonyl]-2-piperidinecarboxamide (286 mg) [see Preparation 40] was added to a solution of triethyloxonium hexafluorophosphate (304 mg) in dichloromethane (5 ml). The reaction mixture was stirred at room temperature for 18 hours after which time the mixture was diluted with dichloromethane and washed with saturated aqueous sodium hydrogen carbonate solution. The organic layer was separated, dried over magnesium sulphate and the solvent was removed under reduced pressure to afford ethyl (2S)-1-[(4-fluorophenyl)sulfonyl]-2-piperidinecarboximidate (290 mg). washed with saturated aqueous sodium hydrogen carbonate solution The organic layer was separated dried over magnesium sulphate the solvent was removed under reduced pressure

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

Procedure: To a solution of (S)-2-(tert-butoxycarbonyl(methyl)amino)-6-methoxy-6-oxohexyl 1H-imidazole-1-carboxylate (2 g, 5.4 mmol) in DCM (10 mL) was added a solution of triethyloxonium hexafluorophosphate (1.61 g, 6.5 mmol, 1.2 equiv.) in DCM (5 mL) dropwise at 0° C. The solution was warmed up to RT and stirred for 15 min. A solution of isoquinolin-3-amine (0.94 g, 6.5 mmol, 1.2 equiv.) in DCM (5 mL) was added. The solution was stirred for overnight. DCM was removed and the residue was purified on RP-HPLC using a mixture of acetonitrile and H2O to give (S)-methyl 5-(tert-butoxycarbonyl(methyl)amino)-6-(isoquinolin-3-ylcarbamoyloxy)hexanoate (1.4 g, 58%). LRMS (M+H+) m/z 446.2. The solution was stirred for overnight DCM was removed the residue was purified on RP-HPLC a mixture of acetonitrile and H2O

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

Procedure: Triethyloxonium hexafluorophosphate (3.20 g, 28.0 mmol) was added to a solution of tert-butyl 3-oxopiperazine-1-carboxylate (2.54 g, 12.7 mmol) in CH2CL2 (31.7 mL) at 0° C., and the resulting solution was stirred at room temperature for 18 hours. The reaction mixture was washed with saturated NaHCO3, dried (Na2SO4), and concentrated to give tert-butyl 3-ethoxy-5,6-dihydropyrazine-1(2H)-carboxylate as an oil. LCMS (APCI+) M+H-t-Bu: 173 (40%); rt=3.14 minutes. The reaction mixture was washed with saturated NaHCO3 dried (Na2SO4) concentrated

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

Procedure: 1.1 ml of N-butylimidazole was introduced into a 50 ml glass flask under an argon atmosphere. 2.08 g of triethyloxonium hexafluorophosphate in solution in 5 ml of 1,2-dichloroethane was then introduced. The mixture was stirred for 4 hours at room temperature. The solvent was evaporated off under vacuum using a vane pump. A colorless liquid was obtained. The solvent was evaporated off under vacuum A colorless liquid was obtained

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The 5-bromo-thiophene 2-carboxylic acid amide (2BW) (7 g, 34.1 mmols) was dissolved in dichloroethane (170 ml). Triethyloxonium hexafluorophosphate (10.16 g, 40.97 mmols) was added and the resulting mixture was refluxed for 1 hr at 90° C. The reaction mixture was concentrated under reduced pressure, and was taken directly to next step. The reaction mixture was concentrated under reduced pressure

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The 5-bromo-thiophene 2-carboxylic acid amide (2BW) (7 g, 34.1 mmols) was dissolved in dichloroethane (170 ml). Triethyloxonium hexafluorophosphate (10.16 g, 40.97 mmols) was added and the resulting mixture was refluxed for 1 hr at 90° C. The reaction mixture was concentrated under reduced pressure, and was taken directly to next step. The reaction mixture was concentrated under reduced pressure

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

Procedure: Triethyloxonium hexafluorophosphate (3.20 g, 28.0 mmol) was added to a solution of tert-butyl 3-oxopiperazine-1-carboxylate (2.54 g, 12.7 mmol) in CH2CL2 (31.7 mL) at 0° C., and the resulting solution was stirred at room temperature for 18 hours. The reaction mixture was washed with saturated NaHCO3, dried (Na2SO4), and concentrated to give tert-butyl 3-ethoxy-5,6-dihydropyrazine-1(2H)-carboxylate as an oil. LCMS (APCI+) M+H−t−Bu: 173 (40%); rt=3.14 minutes. The reaction mixture was washed with saturated NaHCO3 dried (Na2SO4) concentrated

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

Procedure: To a solution of (S)-2-(tert-butoxycarbonyl(methyl)amino)-6-methoxy-6-oxohexyl 1H-imidazole-1-carboxylate (2 g, 5.4 mmol) in DCM (10 mL) was added a solution of triethyloxonium hexafluorophosphate (1.61 g, 6.5 mmol, 1.2 equiv.) in DCM (5 mL) dropwise at 0° C. The solution was warmed up to RT and stirred for 15 min. A solution of isoquinolin-3-amine (0.94 g, 6.5 mmol, 1.2 equiv.) in DCM (5 mL) was added. The solution was stirred for overnight. DCM was removed and the residue was purified on RP-HPLC using a mixture of acetonitrile and H2O to give (S)-methyl 5-(tert-butoxycarbonyl(methyl)amino)-6-(isoquinolin-3-ylcarbamoyloxy)hexanoate (1.4 g, 58%). LRMS (M+H+) m/z 446.2. The solution was stirred for overnight DCM was removed the residue was purified on RP-HPLC a mixture of acetonitrile and H2O

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

Procedure: To a solution of (S)-2-(tert-butoxycarbonyl(methyl)amino)-6-methoxy-6-oxohexyl 1H-imidazole-1-carboxylate (2 g, 5.4 mmol) in DCM (10 mL) was added a solution of triethyloxonium hexafluorophosphate (1.61 g, 6.5 mmol, 1.2 equiv.) in DCM (5 mL) dropwise at 0° C. The solution was warmed up to RT and stirred for 15 min. A solution of isoquinolin-3-amine (0.94 g, 6.5 mmol, 1.2 equiv.) in DCM (5 mL) was added. The solution was stirred for overnight. DCM was removed and the residue was purified on RP-HPLC using a mixture of acetonitrile and H2O to give (S)-methyl 5-(tert-butoxycarbonyl(methyl)amino)-6-(isoquinolin-3-ylcarbamoyloxy)hexanoate (1.4 g, 58%). LRMS (M+H+) m/z 446.2. The solution was stirred for overnight DCM was removed the residue was purified on RP-HPLC a mixture of acetonitrile and H2O

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

Procedure: (2S)-1-[(4-Fluorophenyl)sulfonyl]-2-piperidinecarboxamide (286 mg) [see Preparation 40] was added to a solution of triethyloxonium hexafluorophosphate (304 mg) in dichloromethane (5 ml). The reaction mixture was stirred at room temperature for 18 hours after which time the mixture was diluted with dichloromethane and washed with saturated aqueous sodium hydrogen carbonate solution. The organic layer was separated, dried over magnesium sulphate and the solvent was removed under reduced pressure to afford ethyl (2S)-1-[(4-fluorophenyl)sulfonyl]-2-piperidinecarboximidate (290 mg). washed with saturated aqueous sodium hydrogen carbonate solution The organic layer was separated dried over magnesium sulphate the solvent was removed under reduced pressure