2-bromo-1-(furan-2-yl)ethanone

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

Procedure: The title compound was prepared according to the procedure described in step 2 of Example 1 from 4-chloro-2-(ethoxycarbonylamino)benzonitrile (Example 1, step 1) and 2-bromoacetylfuran (prepared according to the method of S. Kajigaeshi et al., Bull. Chem. Soc. Jpn., 1987, 60, 1159-1160). tlc: Rf=0.4 (33% ethyl acetate in hexanes) prepared

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

Procedure: To a 5 liter round bottomed flask is added 2-acetylfuran (440 grams, 4 moles) and 2.4 liters of ethyl ether at 5 C in an ice bath. To this solution is added, dropwise over a period of two hours, with vigorous stirring, 230 mL bromine (713 grams, 4.46 moles). After the bromine addition is complete, the reaction mixture is stirred for an additional two hours, and then quenched with the addition of 300 mL of water. The mixture is then allowed to separate overnight, and the ether layer is washed with water (3×300 mL), dried over magnesium sulfate, and filtered. Removal of the solvent affords the title product having 1H-NMR (CDCl3) delta 7.53 (t, 1J, J=0.72 Hz), 7.21 (d, 1H, J=3.68 Hz), 6.46 (dd, 1H, J=3.66 Hz and 1.48 Hz), 4.20 (s, 2H). 13C (CDCl3 189.22, 150.12, 147.61, 119.42, 112.93, 30.46 ppm. quenched with the addition of 300 mL of water to separate overnight the ether layer is washed with water (3×300 mL) dried over magnesium sulfate filtered Removal of the solvent

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

Procedure: Bromine (71.14 ml, 1.39 mol) is added dropwise over 1 hour to a solution of 117.59 g (1.07 mol) of 2-acetylfuran (1) in a mixture of 900 ml of either and 400 ml of 1,4-dioxane, at 0° C. under a nitrogen atmosphere. The reaction is warmed to ambient temperature and stirred for 18 hours, then quenched with 1.1 liter of saturated aqueous ammonium chloride and extracted with chloroform. The organic layer is dried over anhydrous magnesium sulfate and concentrated in vacuo to give a dark oil. Flash-chromatography on neutral silica gel using chloroform as eluent followed by distillation using a Kugelruhr apparatus gives 190.81 g (94%) of compound 2 as a light yellow oil, boiling point 85° C. (0.30 mmHg). at 0° C. quenched with 1.1 liter of saturated aqueous ammonium chloride extracted with chloroform The organic layer is dried over anhydrous magnesium sulfate concentrated in vacuo to give a dark oil followed by distillation

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

Procedure: 2-(Bromoacetyl)furan (95 g) is added slowly to a stirred mixture of 75 g of N-methylbenzylamine and 70 g of potassium carbonate in 300 ml of methanol at 20°-30° C. The mixture is stirred at room temperature for 2.5 hours, and the insoluble matter is filtered off. To the filtrate is added 20 g of sodium borohydride at 10°-20° C. with stirring, and the mixture is stirred at room temperature for 3 hours. The solvent is then distilled off under reduced pressure, water is added to the residue, and the separated oil is extracted with ethyl acetate. The extract is washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Distillation of the residue gives 80 g of 2-(N-benzyl-N-methylamino)-1-(2-furyl)ethanol as pale yellow viscous oil, boiling at 130°-138° C. (0.2 mmHg). the insoluble matter is filtered off To the filtrate is added 20 g of sodium borohydride at 10°-20° C. with stirring the mixture is stirred at room temperature for 3 hours The solvent is then distilled off under reduced pressure, water is added to the residue the separated oil is extracted with ethyl acetate The extract is washed with water dried over anhydrous magnesium sulfate concentrated under reduced pressure Distillation of the residue

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

Procedure: The title compound was prepared according to the procedure described in step 2 of Example 1 from 4-chloro-2-(ethoxycarbonylamino)benzonitrile (Example 1, step 1) and 2-bromoacetylfuran (prepared according to the method of S. Kajigaeshi et al., Bull. Chem. Soc. Jpn., 1987, 60, 1159-1160). tlc: Rf=0.4 (33% ethyl acetate in hexanes) prepared

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

Procedure: The title compound was prepared according to the procedure described in step 2 of Example 1 from 4-chloro-2-(ethoxycarbonylamino)benzonitrile (Example 1, step 1) and 2-bromoacetylfuran (prepared according to the method of S. Kajigaeshi et al., Bull. Chem. Soc. Jpn., 1987, 60, 1159-1160). tlc: Rf=0.4 (33% ethyl acetate in hexanes) prepared

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

Procedure: To a 5 liter round bottomed flask is added 2-acetylfuran (440 grams, 4 moles) and 2.4 liters of ethyl ether at 5 C in an ice bath. To this solution is added, dropwise over a period of two hours, with vigorous stirring, 230 mL bromine (713 grams, 4.46 moles). After the bromine addition is complete, the reaction mixture is stirred for an additional two hours, and then quenched with the addition of 300 mL of water. The mixture is then allowed to separate overnight, and the ether layer is washed with water (3×300 mL), dried over magnesium sulfate, and filtered. Removal of the solvent affords the title product having 1H-NMR (CDCl3) delta 7.53 (t, 1J, J=0.72 Hz), 7.21 (d, 1H, J=3.68 Hz), 6.46 (dd, 1H, J=3.66 Hz and 1.48 Hz), 4.20 (s, 2H). 13C (CDCl3 189.22, 150.12, 147.61, 119.42, 112.93, 30.46 ppm. quenched with the addition of 300 mL of water to separate overnight the ether layer is washed with water (3×300 mL) dried over magnesium sulfate filtered Removal of the solvent

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

Procedure: To a 5 liter round bottomed flask is added 2-acetylfuran (440 grams, 4 moles) and 2.4 liters of ethyl ether at 5 C in an ice bath. To this solution is added, dropwise over a period of two hours, with vigorous stirring, 230 mL bromine (713 grams, 4.46 moles). After the bromine addition is complete, the reaction mixture is stirred for an additional two hours, and then quenched with the addition of 300 mL of water. The mixture is then allowed to separate overnight, and the ether layer is washed with water (3×300 mL), dried over magnesium sulfate, and filtered. Removal of the solvent affords the title product having 1H-NMR (CDCl3) delta 7.53 (t, 1J, J=0.72 Hz), 7.21 (d, 1H, J=3.68 Hz), 6.46 (dd, 1H, J=3.66 Hz and 1.48 Hz), 4.20 (s, 2H). 13C (CDCl3 189.22, 150.12, 147.61, 119.42, 112.93, 30.46 ppm. quenched with the addition of 300 mL of water to separate overnight the ether layer is washed with water (3×300 mL) dried over magnesium sulfate filtered Removal of the solvent

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

Procedure: 60% Sodium hydride (320 mg) was suspended in tetrahydrofuran (30 ml), under ice-cooling 2-oxo-3-tert-butoxycarbonylamino-5-pivaloyl-8-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (2.00 g) obtained from Step I of Example 89, and the mixture was stirred for 30 minutes. Bromomethyl(furan-2-yl)ketone (1.89 g) was added dropwise thereto, stirred for 2 hours at room temperature. The reaction mixture was concentrated under reduced pressure, water (100 ml) and ethyl acetate (100 ml) were added, and separated into aqueous layer and organic layer. The aqueous layer was acidified with 1N hydrochloric acid, extracted with ethyl acetate. The extract was combined with the former organic layer. The combined extract was washed with saturated brine, dried over anhydrous magnesium sulfate, subsequently, purified by silica gel column chromatography(chloroform:ethyl acetate=10:1), to thereby obtain 550 mg of the titled compound. stirred for 2 hours at room temperature The reaction mixture was concentrated under reduced pressure, water (100 ml) and ethyl acetate (100 ml) were added separated into aqueous layer and organic layer extracted with ethyl acetate The combined extract was washed with saturated brine dried over anhydrous magnesium sulfate subsequently, purified by silica gel column chromatography(chloroform:ethyl acetate=10:1)

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

Procedure: The title compound is prepared from 2-Bromo-1-furan-2-yl-ethanone and 2-aminobenzothiazole using method B in 30% yield: mp>250° C. (dec); 1H-NMR (DMSO-d6) 6.63 (s, 1H), 6.78 (s, 1H), 7.48 (t, 1H), 7.60 (t, 1H), 7.77 (s, 1H), 8.09 (d, 1H), 8.13 (d, 1H), 8.68 (s, 1H); Anal. (C13H9BrN2OS ⅔ H2O) C, H, N.

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

Procedure: A solution of 2-bromo-1-(2-furyl)ethanone (220 mg, 1.16 mmol) and 6-chloropyridazin-3-amine (150 mg, 1.16 mmol) in dioxane (4 ml) was stirred at room temperature for 1.5 hours, and at 65° C. for 16 hours. The reaction mixture was then cooled to ambient temperature, diluted with 3:1 (chloroform:isopropanol) and water. The layers were separated and the organic layer was concentrated under reduced pressure. Silica gel chromatography (0-15% methanol in dichloromethane) afforded the title compound. The layers were separated the organic layer was concentrated under reduced pressure

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

Procedure: Bromine (71.14 ml, 1.39 mol) is added dropwise over 1 hour to a solution of 117.59 g (1.07 mol) of 2-acetylfuran (1) in a mixture of 900 ml of either and 400 ml of 1,4-dioxane, at 0° C. under a nitrogen atmosphere. The reaction is warmed to ambient temperature and stirred for 18 hours, then quenched with 1.1 liter of saturated aqueous ammonium chloride and extracted with chloroform. The organic layer is dried over anhydrous magnesium sulfate and concentrated in vacuo to give a dark oil. Flash-chromatography on neutral silica gel using chloroform as eluent followed by distillation using a Kugelruhr apparatus gives 190.81 g (94%) of compound 2 as a light yellow oil, boiling point 85° C. (0.30 mmHg). at 0° C. quenched with 1.1 liter of saturated aqueous ammonium chloride extracted with chloroform The organic layer is dried over anhydrous magnesium sulfate concentrated in vacuo to give a dark oil followed by distillation