2,2,3,3,3-pentafluoropropanoyl chloride

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

Procedure: To an ice-cooled, stirred mixture of 3α-hydroxy-5α-pregnan-20-one (260 mg, 318.5 g/m, 0.82 mmol), triethylamine (0.17 mL), and 4-dimethylaminopyridine (DMAP catalytic, 10 mg, 122.17 g/m, 82 umol) dissolved in 17 mL of dry dichloromethane under a nitrogen atmosphere was added pentafluoropropionyl chloride (168 mg, 182.5 g/m 0.92 mmol). The reaction was stirred at 0° C. for 10 hours and then poured into 100 mL of 10% HCl and 200 mL of ether. The organic phase was washed once more with acid, twice with saturated sodium bicarbonate, and then dried over magnesium sulfate. After removal of solvent in vacuo, the crude product was purified by filtration through a bed of silica gel with hexane/ethyl acetate (15:35) elution. The product was isolated from the two earliest fractions (100 mL each) to give (330 mg, 464.5 g/m, 0.71 mmol, 87%). The reaction was stirred at 0° C. for 10 hours The organic phase was washed once more with acid, twice with saturated sodium bicarbonate dried over magnesium sulfate After removal of solvent in vacuo the crude product was purified by filtration through a bed of silica gel with hexane/ethyl acetate (15:35) elution The product was isolated from the two earliest fractions (100 mL each) to give (330 mg, 464.5 g/m, 0.71 mmol, 87%)

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

Procedure: In the test apparatus as described in Example I, and following the procedure of Example I, 75 g (0.315 mole) of CF3CF2CCl3, 100 g 65% oleum (0.80 mole as SO3) and 5 g bromine were heated from 25° C. to 60° C. over a 5 hour period. Fractional distillation of the cold trap product, 50 g, gave 42 g (0.23 mole) of CF3CF2COCl, bp 9° C., for a 73% conversion. were heated from 25° C. to 60° C. over a 5 hour period Fractional distillation of the cold trap product, 50 g

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

Procedure: In the test apparatus as described in Example I, and following the procedure of Example I, 75 g (0.315 mole) of CF3CF2CCl3, 100 g 65% oleum (0.80 mole as SO3) and 5 g bromine were heated from 25° C. to 60° C. over a 5 hour period. Fractional distillation of the cold trap product, 50 g, gave 42 g (0.23 mole) of CF3CF2COCl, bp 9° C., for a 73% conversion. were heated from 25° C. to 60° C. over a 5 hour period Fractional distillation of the cold trap product, 50 g

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: With stirring at −10° C., 17.0 g (93.2 mmol) of pentafluoropropionyl chloride—dissolved in 20 ml of dichloromethane—were added to a mixture of 8.11 g (102 mmol) pyridine and 9.33 g (93.2 mmol) of butyl vinyl ether in 200 ml of dichloromethane. After the addition, stirring was continued at room temperature for a further 15 h. 200 ml of water were then added to the mixture, and the organic phase was separated off, dried and concentrated. This gave 18.9 g (82% of theory) of a yellowish oil. After the addition stirring the organic phase was separated off dried concentrated

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: With stirring at −10° C., 17.0 g (93.2 mmol) of pentafluoropropionyl chloride—dissolved in 20 ml of dichloromethane—were added to a mixture of 8.11 g (102 mmol) pyridine and 9.33 g (93.2 mmol) of butyl vinyl ether in 200 ml of dichloromethane. After the addition, stirring was continued at room temperature for a further 15 h. 200 ml of water were then added to the mixture, and the organic phase was separated off, dried and concentrated. This gave 18.9 g (82% of theory) of a yellowish oil. After the addition stirring the organic phase was separated off dried concentrated

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

Procedure: In a manner similar to that described for Compound 28, a solution of methyl indole-4-carboxylate (351 mg, 2.01 mmol) in dichloroethane (7 mL) was treated with pentafluoropropionyl chloride (2.51 mmol) and aluminum chloride (575 mg). The intermediate ketone (50 mg, 0.16 mmol) in MeOH (2 mL) and conc. HCl (0.02 mL) was treated, as described, with hydrazine hydrate (0.1 mL). The reaction was quenched at 0° C. with 1 M NaOAc and the aqueous layer was adjusted to pH=8 with 1 M NaOH. The product was isolated by extraction with CH2Cl2, and recrystallized (CH2Cl2/MeOH/hexanes) to give 1,5-dihydro-3-pentafluoroethyl-[1,2]diazepino[4,5,6-cd]-indol-6-one, 15 mg (28%) as a yellow solid: 1H NMR (300 MHz, d6-DMSO) δ 7.16 (app br t, 1H), 7.54 (m, 2H), 7.65 (m, 1H), 10.87 (s, 1H), 12.15 (s, 1H). HRMS (FAB, Mna+) Calcd for C11H10N3Ona: 352.0674. Found: 352.0668. The reaction was quenched at 0° C. with 1 M NaOAc The product was isolated by extraction with CH2Cl2 recrystallized (CH2Cl2/MeOH/hexanes)

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

Procedure: In a manner similar to that described for Compound 28, a solution of methyl indole-4-carboxylate (351 mg, 2.01 mmol) in dichloroethane (7 mL) was treated with pentafluoropropionyl chloride (2.51 mmol) and aluminum chloride (575 mg). The intermediate ketone (50 mg, 0.16 mmol) in MeOH (2 mL) and conc. HCl (0.02 mL) was treated, as described, with hydrazine hydrate (0.1 mL). The reaction was quenched at 0° C. with 1 M NaOAc and the aqueous layer was adjusted to pH=8 with 1 M NaOH. The product was isolated by extraction with CH2Cl2, and recrystallized (CH2Cl2/MeOH/hexanes) to give 1,5-dihydro-3-pentafluoroethyl-[1,2]diazepino[4,5,6-cd]-indol-6-one, 15 mg (28%) as a yellow solid: 1H NMR (300 MHz, d6-DMSO) δ 7.16 (app br t, 1H), 7.54 (m, 2H), 7.65 (m, 1H), 10.87 (s, 1H), 12.15 (s, 1H). HRMS (FAB, Mna+) Calcd for C11H10N3Ona: 352.0674. Found: 352.0668. The reaction was quenched at 0° C. with 1 M NaOAc The product was isolated by extraction with CH2Cl2 recrystallized (CH2Cl2/MeOH/hexanes)

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

Procedure: To an ice-cooled, stirred mixture of 3α-hydroxy-5α-pregnan-20-one (260 mg, 318.5 g/m, 0.82 mmol), triethylamine (0.17 mL), and 4-dimethylaminopyridine (DMAP catalytic, 10 mg, 122.17 g/m, 82 umol) dissolved in 17 mL of dry dichloromethane under a nitrogen atmosphere was added pentafluoropropionyl chloride (168 mg, 182.5 g/m 0.92 mmol). The reaction was stirred at 0° C. for 10 hours and then poured into 100 mL of 10% HCl and 200 mL of ether. The organic phase was washed once more with acid, twice with saturated sodium bicarbonate, and then dried over magnesium sulfate. After removal of solvent in vacuo, the crude product was purified by filtration through a bed of silica gel with hexane/ethyl acetate (15:35) elution. The product was isolated from the two earliest fractions (100 mL each) to give (330 mg, 464.5 g/m, 0.71 mmol, 87%). The reaction was stirred at 0° C. for 10 hours The organic phase was washed once more with acid, twice with saturated sodium bicarbonate dried over magnesium sulfate After removal of solvent in vacuo the crude product was purified by filtration through a bed of silica gel with hexane/ethyl acetate (15:35) elution The product was isolated from the two earliest fractions (100 mL each) to give (330 mg, 464.5 g/m, 0.71 mmol, 87%)

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

Procedure: In a manner similar to that described for Compound 28, a solution of methyl indole-4-carboxylate (351 mg, 2.01 mmol) in dichloroethane (7 mL) was treated with pentafluoropropionyl chloride (2.51 mmol) and aluminum chloride (575 mg). The intermediate ketone (50 mg, 0.16 mmol) in MeOH (2 mL) and conc. HCl (0.02 mL) was treated, as described, with hydrazine hydrate (0.1 mL). The reaction was quenched at 0° C. with 1 M NaOAc and the aqueous layer was adjusted to pH=8 with 1 M NaOH. The product was isolated by extraction with CH2Cl2, and recrystallized (CH2Cl2/MeOH/hexanes) to give 1,5-dihydro-3-pentafluoroethyl-[1,2]diazepino[4,5,6-cd]-indol-6-one, 15 mg (28%) as a yellow solid: 1H NMR (300 MHz, d6-DMSO) δ 7.16 (app br t, 1H), 7.54 (m, 2H), 7.65 (m, 1H), 10.87 (s, 1H), 12.15 (s, 1H). HRMS (FAB, Mna+) Calcd for C11H10N3Ona: 352.0674. Found: 352.0668. The reaction was quenched at 0° C. with 1 M NaOAc The product was isolated by extraction with CH2Cl2 recrystallized (CH2Cl2/MeOH/hexanes)

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

Procedure: In a manner similar to that described for Compound 28, a solution of methyl indole-4-carboxylate (351 mg, 2.01 mmol) in dichloroethane (7 mL) was treated with pentafluoropropionyl chloride (2.51 mmol) and aluminum chloride (575 mg). The intermediate ketone (50 mg, 0.16 mmol) in MeOH (2 mL) and conc. HCl (0.02 mL) was treated, as described, with hydrazine hydrate (0.1 mL). The reaction was quenched at 0° C. with 1 M NaOAc and the aqueous layer was adjusted to pH=8 with 1 M NaOH. The product was isolated by extraction with CH2Cl2, and recrystallized (CH2Cl2/MeOH/hexanes) to give 1,5-dihydro-3-pentafluoroethyl-[1,2]diazepino[4,5,6-cd]-indol-6-one, 15 mg (28%) as a yellow solid: 1H NMR (300 MHz, d6-DMSO) δ 7.16 (app br t, 1H), 7.54 (m, 2H), 7.65 (m, 1H), 10.87 (s, 1H), 12.15 (s, 1H). HRMS (FAB, Mna+) Calcd for C11H10N3Ona: 352.0674. Found: 352.0668. The reaction was quenched at 0° C. with 1 M NaOAc The product was isolated by extraction with CH2Cl2 recrystallized (CH2Cl2/MeOH/hexanes)

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

Procedure: In a manner similar to that described for Compound 28, a solution of methyl indole-4-carboxylate (351 mg, 2.01 mmol) in dichloroethane (7 mL) was treated with pentafluoropropionyl chloride (2.51 mmol) and aluminum chloride (575 mg). The intermediate ketone (50 mg, 0.16 mmol) in MeOH (2 mL) and conc. HCl (0.02 mL) was treated, as described, with hydrazine hydrate (0.1 mL). The reaction was quenched at 0° C. with 1 M NaOAc and the aqueous layer was adjusted to pH=8 with 1 M NaOH. The product was isolated by extraction with CH2Cl2, and recrystallized (CH2Cl2/MeOH/hexanes) to give 1,5-dihydro-3-pentafluoroethyl-[1,2]diazepino[4,5,6-cd]-indol-6-one, 15 mg (28%) as a yellow solid: 1H NMR (300 MHz, d6-DMSO) 7.16 (app br t, 1H), 7.54 (m, 2H), 7.65 (m, 1H), 10.87 (s, 1H), 12.15 (s, 1H). HRMS (FAB, Mna+) Calcd for C11H10N3Ona: 352.0674. Found: 352.0668. The reaction was quenched at 0° C. with 1 M NaOAc The product was isolated by extraction with CH2Cl2 recrystallized (CH2Cl2/MeOH/hexanes)

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

Procedure: To an ice-cooled, stirred mixture of 3α-hydroxy-5α-pregnan-20-one (260 mg, 318.5 g/m, 0.82 mmol), triethylamine (0.17 mL), and 4-dimethylaminopyridine (DMAP catalytic, 10 mg, 122.17 g/m, 82 umol) dissolved in 17 mL of dry dichloromethane under a nitrogen atmosphere was added pentafluoropropionyl chloride (168 mg, 182.5 g/m 0.92 mmol). The reaction was stirred at 0° C. for 10 hours and then poured into 100 ml of 10% HCl and 200 ml of ether. The organic phase was washed once more with acid, twice with saturated sodium bicarbonate, and then dried over magnesium sulfate. After removal of solvent in vacuo, the crude product was purified by filtration through a bed of silica gel with hexane/ethyl acetate (15:35) elution. The product was isolated from the two earliest fractions (100 mL each) to give (330 mg, 464.5 g/m, 0.71 mmol, 87%). The reaction was stirred at 0° C. for 10 hours The organic phase was washed once more with acid, twice with saturated sodium bicarbonate dried over magnesium sulfate After removal of solvent in vacuo the crude product was purified by filtration through a bed of silica gel with hexane/ethyl acetate (15:35) elution The product was isolated from the two earliest fractions (100 mL each) to give (330 mg, 464.5 g/m, 0.71 mmol, 87%)