2,2,3,3,3-pentafluoropropanoyl 2,2,3,3,3-pentafluoropropanoate

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

Procedure: In a manner similar to that of Example 1, H2O2 (>95%) was combined with pentafluoropropionic anhydride to give bis(pentafluoropropanoyl) peroxide (δ−85.1, −121.3) in pentafluoropropionic acid.

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

Procedure: In 10 ml of acetonitrile was suspended 687 mg (2.0 mM) of 4,5-dihydro-4-(piperidin-4-ylmethyl)-3H-1,4,8b-triazaacenaphthylen-3-one dihydrochloride, followed by addition of 2.23 ml (16.0 mM) of triethylamine and 1.97 ml (10.0 mM) of pentafluoropropionic anhydride in the order mentioned. This mixture was stirred at room temperature for 1 hour and the solvent was then distilled off under reduced pressure. The residue was extracted with 50 ml of chloroform and the organic layer was washed with 50 ml of saturated aqueous NaCl solution and dried over MgSO4. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (eluent: ethyl acetate-ethanol=10:1) to provide 526 mg (yield 63.2%) of the title compound as light-yellow amorphous substance. the solvent was then distilled off under reduced pressure The residue was extracted with 50 ml of chloroform the organic layer was washed with 50 ml of saturated aqueous NaCl solution dried over MgSO4 The solvent was distilled off under reduced pressure the residue was purified by silica gel column chromatography (eluent: ethyl acetate-ethanol=10:1)

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

Procedure: In 10 ml of acetonitrile was suspended 687 mg (2.0 mM) of 4,5-dihydro-4-(piperidin-4-ylmethyl)-3H-1,4,8b-triazaacenaphthylen-3-one dihydrochloride, followed by addition of 2.23 ml (16.0 mM) of triethylamine and 1.97 ml (10.0 mM) of pentafluoropropionic anhydride in the order mentioned. This mixture was stirred at room temperature for 1 hour and the solvent was then distilled off under reduced pressure. The residue was extracted with 50 ml of chloroform and the organic layer was washed with 50 ml of saturated aqueous NaCl solution and dried over MgSO4. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (eluent: ethyl acetate-ethanol=10:1) to provide 526 mg (yield 63.2%) of the title compound as light-yellow amorphous substance. the solvent was then distilled off under reduced pressure The residue was extracted with 50 ml of chloroform the organic layer was washed with 50 ml of saturated aqueous NaCl solution dried over MgSO4 The solvent was distilled off under reduced pressure the residue was purified by silica gel column chromatography (eluent: ethyl acetate-ethanol=10:1)

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

Procedure: To a solution of (R)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethanamine (15 mg, 0.038 mmol), prepared by method described in Procedures 5, 6 and 7, in anhydrous DCM (0.5 mL), was added pyridine (1 drop) and 2,2,3,3,3-pentafluoropropanoic anhydride (14 mg, 0.040 mmol) at room temperature. The reaction mixture was stirred for 5 mins and the solvents removed under a stream of nitrogen. The resulting residue was diluted with MeOH (0.5 mL) and purified by preparative HPLC (YMC Sunfire 30×100 mm column, eluting with 10-90% MeOH/H2O over 10 minutes containing 0.1% TFA; 40 mL/min, monitoring at 220 nm); (R)-N-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-2,2,3,3,3-pentafluoropropanamide (13.4 mg, 65% yield) was isolated as a colorless oil at a retention time of 12.44 min. LCMS: RT=2.12 min [M+H] 541.21 (LCMS Method 2); HPLC: RT=4.28 min, Purity 98% (HPLC Method 1) NMR: 400 MHz 1H (CDCl3) 9.60 ppm, 1 H, s; 8.36 ppm, 1 H, s; 7.75 ppm, 1H, d, J=8.0 Hz; 7.44 ppm, 1H, s; 7.34 ppm, 1H, d, J=8.0Hz; 7.30 ppm, 1H, d, J=8.0 Hz; 7.09 ppm, 4 H, m; 6.53 ppm, 2H, d, J=4.0 Hz; 3.38 ppm, 1H, d, J=12.0 Hz; 3.65 ppm, 1H, d, J=12.0 Hz. the solvents removed under a stream of nitrogen The resulting residue was diluted with MeOH (0.5 mL) purified by preparative HPLC (YMC Sunfire 30×100 mm column, eluting with 10-90% MeOH/H2O over 10 minutes containing 0.1% TFA; 40 mL/min, monitoring at 220 nm)

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

Procedure: In a manner similar to that of Example 1, H2O2 (>95%) was combined with pentafluoropropionic anhydride to give bis(pentafluoropropanoyl) peroxide (δ−85.1, −121.3) in pentafluoropropionic acid.

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

Procedure: In 10 ml of acetonitrile was suspended 687 mg (2.0 mM) of 4,5-dihydro-4-(piperidin-4-ylmethyl)-3H-1,4,8b-triazaacenaphthylen-3-one dihydrochloride, followed by addition of 2.23 ml (16.0 mM) of triethylamine and 1.97 ml (10.0 mM) of pentafluoropropionic anhydride in the order mentioned. This mixture was stirred at room temperature for 1 hour and the solvent was then distilled off under reduced pressure. The residue was extracted with 50 ml of chloroform and the organic layer was washed with 50 ml of saturated aqueous NaCl solution and dried over MgSO4. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (eluent: ethyl acetate-ethanol=10:1) to provide 526 mg (yield 63.2%) of the title compound as light-yellow amorphous substance. the solvent was then distilled off under reduced pressure The residue was extracted with 50 ml of chloroform the organic layer was washed with 50 ml of saturated aqueous NaCl solution dried over MgSO4 The solvent was distilled off under reduced pressure the residue was purified by silica gel column chromatography (eluent: ethyl acetate-ethanol=10:1)

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

Procedure: In 10 ml of acetonitrile was suspended 687 mg (2.0 mM) of 4,5-dihydro-4-(piperidin-4-ylmethyl)-3H-1,4,8b-triazaacenaphthylen-3-one dihydrochloride, followed by addition of 2.23 ml (16.0 mM) of triethylamine and 1.97 ml (10.0 mM) of pentafluoropropionic anhydride in the order mentioned. This mixture was stirred at room temperature for 1 hour and the solvent was then distilled off under reduced pressure. The residue was extracted with 50 ml of chloroform and the organic layer was washed with 50 ml of saturated aqueous NaCl solution and dried over MgSO4. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (eluent: ethyl acetate-ethanol=10:1) to provide 526 mg (yield 63.2%) of the title compound as light-yellow amorphous substance. the solvent was then distilled off under reduced pressure The residue was extracted with 50 ml of chloroform the organic layer was washed with 50 ml of saturated aqueous NaCl solution dried over MgSO4 The solvent was distilled off under reduced pressure the residue was purified by silica gel column chromatography (eluent: ethyl acetate-ethanol=10:1)