2,3,4,5,6-pentafluorobenzoyl chloride

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Beginning with 0.010 gm (0.044 mMol) 5-amino-3-(1-methylpiperidin-4-yl)pyrrolo[3,2-b]pyridine and 0.008 mL (0.053 mMol) 2,3,4,5,6-pentafluorobenzoyl chloride, 0.016 gm (84%) of the title compound were prepared essentially by the procedure described in Example 7.

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

Procedure: A 7.35 g portion of magnesium chips, 1 5 ml of carbon tetrachloride and 15 ml of absolute ethanol were added to a dry flask. A solution of 48.1 g of diethyl malonate in 30 ml of absolute ethanol and 120 ml of anhydrous ether was added dropwise over a one hour period. When addition was complete, the mixture was stirred at reflux for 3 hours then cooled to -10° C. with dry ice/acetone. A solution of 70 g of pentafluorobenzoyl chloride in 120 ml of ether was added over 2 hours, maintaining the temperature at not more than -5° C. The mixture was then stirred overnight at room temperature, partially evaporated, cooled in crushed ice and an ice cold solution of 7.5 ml of concentrated sulfuric acid in 300 ml of Water was added at a rate such that the internal temperature did not go above 5° C. The mixture was extracted several times with ether, the extracts combined, washed with saturated sodium chloride, dried and concentrated, giving 106 g of (pentafluorobenzoyl)propanedioic acid, diethyl ester as a yellow oil. When addition at reflux for 3 hours maintaining the temperature at not more than -5° C The mixture was then stirred overnight at room temperature partially evaporated cooled in crushed ice an ice cold solution of 7.5 ml of concentrated sulfuric acid in 300 ml of Water was added at a rate such that the internal temperature did not go above 5° C The mixture was extracted several times with ether washed with saturated sodium chloride dried concentrated

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

Procedure: A 7.35 g portion of magnesium chips, 1 5 ml of carbon tetrachloride and 15 ml of absolute ethanol were added to a dry flask. A solution of 48.1 g of diethyl malonate in 30 ml of absolute ethanol and 120 ml of anhydrous ether was added dropwise over a one hour period. When addition was complete, the mixture was stirred at reflux for 3 hours then cooled to -10° C. with dry ice/acetone. A solution of 70 g of pentafluorobenzoyl chloride in 120 ml of ether was added over 2 hours, maintaining the temperature at not more than -5° C. The mixture was then stirred overnight at room temperature, partially evaporated, cooled in crushed ice and an ice cold solution of 7.5 ml of concentrated sulfuric acid in 300 ml of Water was added at a rate such that the internal temperature did not go above 5° C. The mixture was extracted several times with ether, the extracts combined, washed with saturated sodium chloride, dried and concentrated, giving 106 g of (pentafluorobenzoyl)propanedioic acid, diethyl ester as a yellow oil. When addition at reflux for 3 hours maintaining the temperature at not more than -5° C The mixture was then stirred overnight at room temperature partially evaporated cooled in crushed ice an ice cold solution of 7.5 ml of concentrated sulfuric acid in 300 ml of Water was added at a rate such that the internal temperature did not go above 5° C The mixture was extracted several times with ether washed with saturated sodium chloride dried concentrated

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

Procedure: 4-Aminomethyl-7-diethylaminocoumarin (50 mg, 0.2 mmol) is treated with pentafluorobenzoyl chloride (0.5 mL, 0.3 mmol) at 0° C. under dry argon protection, and worked up according to the procedure of Example 25. Compound 29 is obtained as an off-white solid (67 mg, yield: 76%).

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

Procedure: Beginning with 0.010 gm (0.044 mMol) 5-amino-3-(1-methylpiperidin-4-yl)pyrrolo[3,2-b]pyridine and 0.008 mL (0.053 mMol) 2,3,4,5,6-pentafluorobenzoyl chloride, 0.016 gm (84%) of the title compound was prepared essentially by the procedure described in Example 7.

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

Procedure: Following the general procedure described above, reaction of pentafluorobenzoyl chloride (6.92 g, 30.0 mmol) with 2-mercaptopyridine (3.33 g, 30.0 mmol) in THF (30 mL) for 30 min at room temperature afforded pale yellow solid after precipitation (7.97 g, 87%): mp 51° C.; 1H NMR δ 7.37-7.42 (m, 1H), 7.75-7.79 (m, 1H), 7.81-7.87 (m, 1H), 8.67-8.71 (m, 1H); Anal. Calcd for C12H4NOS: C, 47.22; H, 1.32; N, 4.59. Found: C, 47.59; H, 1.29; N, 4.38. afforded pale yellow solid after precipitation (7.97 g, 87%)

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

Procedure: Beginning with 0.010 gm (0.044 mMol) 5-amino-3-(1-methylpiperidin-4-yl)pyrrolo[3,2-b]pyridine and 0.008 mL (0.053 mMol) 2,3,4,5,6-pentafluorobenzoyl chloride, 0.016 gm (84%) of the title compound were prepared essentially by the procedure described in Example 7.

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

Procedure: Into a 250 ml three-neck flask, which was equipped with an additional funnel and calcium chloride drying tube, were placed 4-ethoxydiphenyl ether (3.5 g), which was synthesized from p-phenoxyphenol with ethyl iodide in the presence of sodium hydroxide, aluminum chloride (5.4 g) and dried dichloroethane (30 ml). The solution of 2,3,4,5,6-pentafluorobenzoyl chloride (3.7 g), which was synthesized from 2,3,4,5,6-pentafluorobenzoic acid with thionyl chloride, and dried dichloroethane (10 ml) was slowly dripped into flask while stirring. After the addition was complete, the reaction mixture was stirred overnight at room temperature. Small amount of water was added very slowly to the reaction mixture and continued stirring for 15 min. The reaction mixture was then poured into 250 ml of water, which was extracted with dichloromethane. The organic layer was collected, washed with water, dried over sodium sulfate, filtered and evaporated. Recrystallization from methanol with charcoal yielded white crystal of 4-ethyoxy-4′-(2,3,4,5,6-pentafluorobenzoyl) diphenyl ehter (EPDE) (yield 60.4%). Into a 250 ml three-neck flask, which was equipped with an additional funnel and calcium chloride drying tube was slowly dripped into flask After the addition the reaction mixture was stirred overnight at room temperature continued stirring for 15 min was extracted with dichloromethane The organic layer was collected washed with water dried over sodium sulfate filtered evaporated Recrystallization from methanol with charcoal yielded white crystal of 4-ethyoxy-4′-(2,3,4,5,6-pentafluorobenzoyl) diphenyl ehter (EPDE) (yield 60.4%)

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

Procedure: To a mixture of perfluorobenzoyl chloride (2.51 g, 10.9 mmol) and 2-bromothiophene (1.86 g, 11.4 mmol) in carbon disulfide (80 mL), aluminum chloride (2.90 g, 21.8 mmol) was added in portions over 10 min with vigorous mechanical stirring. The reaction mixture turned red and was stirred for 2.5 h before being quenched with water (80 mL). The organics were then separated, the aqueous layer extracted with carbon disulfide (3×50 mL), and the combined organics washed with water (3×100 mL) and dried over MgSO4. After filtration, the organics were concentrated in vacuo and the chromatographed on a silica gel column (hexane:ether=9:1) to yield 1.23 g (32%) green crystals. mp 51-54° C.; 1H NMR (DMSO): δ 7.78 (d, 2H, 3J=3.6 Hz), 7.54 (d, 2H, 3J=4.4 Hz); 19F NMR (DMSO): δ −142.1 (m, 2H), −151.6 (m, 1H), −160.6 (m, 2H) Anal. Calcd for C11H2BrF5OS: C 37.00, H 0.56. Found: C 37.37, H 0.83; MS (EI): m/z (%) 355.8 (92) [M+]. was added in portions over 10 min with vigorous mechanical stirring before being quenched with water (80 mL) The organics were then separated the aqueous layer extracted with carbon disulfide (3×50 mL) the combined organics washed with water (3×100 mL) dried over MgSO4 After filtration the organics were concentrated in vacuo the chromatographed on a silica gel column (hexane:ether=9:1)

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

Procedure: To a mixture of perfluorobenzoyl chloride (2.51 g, 10.9 mmol) and 2-bromothiophene (1.86 g, 11.4 mmol) in carbon disulfide (80 mL), aluminum chloride (2.90 g, 21.8 mmol) was added in portions over 10 min with vigorous mechanical stirring. The reaction mixture turned red and was stirred for 2.5 h before being quenched with water (80 mL). The organics were then separated, the aqueous layer extracted with carbon disulfide (3×50 mL), and the combined organics washed with water (3×100 mL) and dried over MgSO4. After filtration, the organics were concentrated in vacuo and the chromatographed on a silica gel column (hexane:ether=9:1) to yield 1.23 g (32%) green crystals. mp 51-54° C.; 1H NMR (DMSO): δ 7.78 (d, 2H, 3J=3.6 Hz), 7.54 (d, 2H, 3J=4.4 Hz); 19F NMR (DMSO): δ −142.1 (m, 2H), −151.6 (m, 1H), −160.6 (m, 2H) Anal. Calcd for C11H2BrF5OS: C 37.00, H 0.56. Found: C 37.37, H 0.83; MS (EI): m/z (%) 355.8 (92) [M+]. was added in portions over 10 min with vigorous mechanical stirring before being quenched with water (80 mL) The organics were then separated the aqueous layer extracted with carbon disulfide (3×50 mL) the combined organics washed with water (3×100 mL) dried over MgSO4 After filtration the organics were concentrated in vacuo the chromatographed on a silica gel column (hexane:ether=9:1)