5-(2-bromoethyl)-3H-2-benzofuran-1-one

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a flask containing 1-(piperazin-1-ylmethyl)-2,3-dihydro-1H-indene-4-carbonitrile (0.04 g, 0.17 mmol) was added 5-(2-bromoethyl)-2-benzofuran-1-(3H)-one (0.02 g, 0.06 mmol), tetrabutyl ammonium iodide (0.02 g, 0.06 mmol) and morpholine (0.08 mL, 0.99 mmol); the resulting mixture was dissolved in DMF (3 mL) and stirred at 60° C. Analysis of the reaction mixture indicated that reaction had gone to completion. The solution was concentrated in vacuo and shot into Mass-directed HPLC for separation to give the desired 1-({4-[2-(3-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]piperazin-1-yl}methyl)indane-4-carbonitrile. LC-MS (IE, m/z): 402 [M+1]+. (0.27 μM) Analysis of the reaction mixture indicated that reaction The solution was concentrated in vacuo shot into Mass-directed HPLC for separation

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 6-Piperazin-1-yl-5,6,7,8-tetrahydronaphtho[2,3-c][1,2,5]oxadiazole hydrochloride (20 mg, 0.068 mmol), 5-(2-bromoethyl)-2-benzofuran-1(3H)-one (33 mg, 0.14 mmol), and tetrabutylammonium iodide (2.5 mg, 6.8 umol) in DMF (2 mL) was added triethylamine (0.028 mL, 0.20 mmol). The mixture was heated to 55° C. for 6 hours. LC showed formation of the desired product, which was separated by mass-directed HPLC. LC-MS (IE, m/z): 419 [M+1]+. (0.21 μM)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-(2-hydroxyethyl)-2-benzofuran-1(3H)-one (1.2 g, 6.8 mmol) in DCM at 0° C. was added carbon tetrabromide (2.3 g, 6.8 mmol), triphenylphosphine (1.8 g, 6.8 mmol), and imidazole (0.46 g, 6.8 mmol). The mixture was allowed to stir at 0° C. for 5 minutes, and then allowed to warm to RT and stir for 1.5 hours. The crude was concentrated and purified by silica gel chromatography (43% EtOAc with Hexanes). About 1.3 grams of 5-(2-Bromoethyl)-2-benzofuran-1(3H)-one was collected as a white solid. LC-MS (IE, m/z): 241/243 (M+1)+. to warm to RT stir for 1.5 hours The crude was concentrated purified by silica gel chromatography (43% EtOAc with Hexanes) About 1.3 grams of 5-(2-Bromoethyl)-2-benzofuran-1(3H)-one was collected as a white solid

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-[2-(1-Oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]piperazin-2-one (30 mg, 0.12 mmol) and 5-(2-Bromoethyl)-2-benzofuran-1(3H)-one (56 mg, 0.23 mmol) in DMF (2 ml) was added TEA (0.048 ml, 0.35 mmol) and tetrabutylammonium iodide (4.3 mg, 0.012 mmol). The mixture was heated to 55° C. for 16 hours. LC showed formation of the desired product, which was purified by mass-directed reverse phase HPLC (AcCN-Water with 0.1% TFA). LC-MS (IE, m/z): 421 [M+1]+.

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-[2-(2,1,3-Benzoxadiazol-5-yl)ethyl]piperazin-2-one (54 mg, 0.22 mmol), 5-(2-Bromoethyl)-2-benzofuran-1(3H)-one (105 mg, 0.44 mol), Triethylamine (0.15 mL, 1.1 mmol), and DMF (1.5 mL) was heated to 60° C. for 24 hours. The reaction was diluted with EtOAc, washed with water and brine, dried over MgSO4, and purified by prep-TLC (5% MeOH in DCM) to deliver the title product. LC-MS (IE, m/z): 407 [M+1]+. washed with water and brine dried over MgSO4 purified by prep-TLC (5% MeOH in DCM)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-(2-hydroxyethyl)-2-benzofuran-1(3H)-one (1.2 g, 6.8 mmol) in DCM at 0° C. was added carbon tetrabromide (2.3 g, 6.8 mmol), triphenylphosphine (1.8 g, 6.8 mmol), and imidazole (0.46 g, 6.8 mmol). The mixture was allowed to stir at 0° C. for 5 minutes, and then allowed to warm to RT and stir for 1.5 hours. The crude was concentrated and purified by silica gel chromatography (43% EtOAc with Hexanes) to obtain 5-(2-Bromoethyl)-2-benzofuran-1(3H)-one. LC-MS (IE, m/z): 241/243 (M+1)+. to warm to RT stir for 1.5 hours The crude was concentrated purified by silica gel chromatography (43% EtOAc with Hexanes)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-(2-hydroxyethyl)-2-benzofuran-1(3H)-one (1.2 g, 6.8 mmol) in DCM at 0° C. was added carbon tetrabromide (2.3 g, 6.8 mmol), triphenylphosphine (1.8 g, 6.8 mmol), and imidazole (0.46 g, 6.8 mmol). The mixture was allowed to stir at 0° C. for 5 minutes, and then allowed to warm to RT and stir for 1.5 hours. The crude was concentrated and purified by silica gel chromatography (43% EtOAc with Hexanes) to obtain 5-(2-Bromoethyl)-2-benzofuran-1(3H)-one. LC-MS (IE, m/z): 241/243 (M+1)+. to warm to RT stir for 1.5 hours The crude was concentrated purified by silica gel chromatography (43% EtOAc with Hexanes)