2,2-dimethyl-3H-1-benzofuran-7-amine

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

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

Procedure: A stirred solution of 10.0 grams (0.061 mole) of 7-amino-2,3-dihydro-2,2-dimethylbenzofuran in 150 mL of N,N-dimethylformamide was cooled in an ice-water bath, and asolution of 10.9 grams (0.061 mole) of N-bromosuccinimide in 50 mL of N,N-dimethylformamide was added in one portion. Upon completion of addition, the reaction mixture was maintained in the ice-water bath for about one hour. After this time the reaction mixture was poured into about 600 mL of water. The mixture was then extracted with two 200 mL portions of diethyl ether. The combined extracts were washed with two 100 mL portions of an aqueous 10% lithium chloride solution. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, yielding 12.3 grams of 7-amino-4-bromo-2,3-dihydro-2,2-dimethylbenzofuran. The NMR spectrum was consistent with the proposed structure. Upon completion of addition The mixture was then extracted with two 200 mL portions of diethyl ether The combined extracts were washed with two 100 mL portions of an aqueous 10% lithium chloride solution The organic layer was dried with magnesium sulfate filtered The filtrate was concentrated under reduced pressure

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

Procedure: A diazonium salt was prepared by adding 13.8 g of sodium nitrite to a suspension of 32.6 g of 7-amino-2,3-dihydro-2,2-dimethylbenzofuran and 40 ml of concentrated sulfuric acid in 200 ml water cooled 0° to 5° C. After stirring for about 0.4 hour at 0° to 5° C., the diazonium salt suspension was poured in one portion into a mixture consisting of 170 ml of acetic acid, 40 ml of concentrated hydrochloric acid, 17 g of cupric chloride dihydrate and 30 ml of sulfur dioxide and cooled by 10° C. by an ice-water bath. The mixture was stirred about 1 hour at 15° to 25° C. Then 400 ml of 1-chlorobutane and 200 ml of water was added and the mixture was stirred and heated at 35° C. for 5 hours. After cooling to room temperature, the organic layer was separated, washed with saturated aqueous NaHCO3 and water, and dried over sodium sulfate for 0.5 hour. The solvent was evaporated under reduced pressure at less than 45° C. to give 26 g of crude 2,3-dihydro-2,2-dimethyl-7-benzofuransulfonyl chloride as an oil. cooled 0° to 5° C The mixture was stirred about 1 hour at 15° to 25° C the mixture was stirred heated at 35° C. for 5 hours After cooling to room temperature the organic layer was separated washed with saturated aqueous NaHCO3 and water dried over sodium sulfate for 0.5 hour The solvent was evaporated under reduced pressure at less than 45° C.

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

Procedure: A diazonium salt was prepared by adding 13.8 g of sodium nitrite to a suspension of 32.6 g of 7-amino-2,3-dihydro-2,2-dimethylbenzofuran and 40 ml of concentrated sulfuric acid in 200 ml water cooled 0° to 5° C. After stirring for about 0.4 hour at 0° to 5° C., the diazonium salt suspension was poured in one portion into a mixture consisting of 170 ml of acetic acid, 40 ml of concentrated hydrochloric acid, 17 g of cupric chloride dihydrate and 30 ml of sulfur dioxide and cooled by 10° C. by an ice-water bath. The mixture was stirred about 1 hour at 15° to 25° C. Then 400 ml of 1-chlorobutane and 200 ml of water was added and the mixture was stirred and heated at 35° C. for 5 hours. After cooling to room temperature, the organic layer was separated, washed with saturated aqueous NaHCO3 and water, and dried over sodium sulfate for 0.5 hour. The solvent was evaporated under reduced pressure at less than 45° C. to give 26 g of crude 2,3-dihydro-2,2-dimethyl-7-benzofuransulfonyl chloride as an oil. cooled 0° to 5° C The mixture was stirred about 1 hour at 15° to 25° C the mixture was stirred heated at 35° C. for 5 hours After cooling to room temperature the organic layer was separated washed with saturated aqueous NaHCO3 and water dried over sodium sulfate for 0.5 hour The solvent was evaporated under reduced pressure at less than 45° C.

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

Procedure: A stirred solution of 10.0 grams (0.061 mole) of 7-amino-2,3-dihydro-2,2-dimethylbenzofuran in 150 mL of N,N-dimethylformamide is cooled in an ice-water bath, and a solution of 10.9 grams (0.061 mole) of N-bromosuccinimide in 50 mL of N,N-dimethylformamide is added in one portion. Upon completion of addition, the reaction mixture is maintained in the ice-water bath for about one hour After this time the reaction mixture is poured into about 600 mL of water. The mixture is then extracted with two 200 mL portions of diethyl ether. The combined extracts are washed with two 100 mL portions of an aqueous 10% lithium chloride solution. The organic layer is dried with magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure, yielding 12.3 grams of 7-amino-4-bromo-2,3-dihydro-2,2-dimethylbenzofuran. The NMR spectrum is consistent with the proposed structure. Upon completion of addition The mixture is then extracted with two 200 mL portions of diethyl ether The combined extracts are washed with two 100 mL portions of an aqueous 10% lithium chloride solution The organic layer is dried with magnesium sulfate filtered The filtrate is concentrated under reduced pressure

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

Procedure: A stirred solution of 10.0 grams (0.061 mole) of 7-amino-2,3-dihydro-2,2-dimethylbenzofuran in 150 mL of N,N-dimethylformamide is cooled in an ice-water bath, and a solution of 10.9 grams (0.061 mole) of N-bromosuccinimide in 50 mL of N,N-dimethylformamide is added in one portion. Upon completion of addition, the reaction mixture is maintained in the ice-water bath for about one hour After this time the reaction mixture is poured into about 600 mL of water. The mixture is then extracted with two 100 mL portions of diethyl ether. The combined extracts are washed with two 100 mL portions of an aqueous 10% lithium chloride solution. The organic layer is dried with magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure, yielding 12.3 grams of 7-amino-4-bromo-2,3-dihydro-2,2-dimethylbenzofuran. The NMR spectrum is consistent with the proposed structure. Upon completion of addition The mixture is then extracted with two 100 mL portions of diethyl ether The combined extracts are washed with two 100 mL portions of an aqueous 10% lithium chloride solution The organic layer is dried with magnesium sulfate filtered The filtrate is concentrated under reduced pressure

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

Procedure: In the same manner as in Example 19, step 5 and using 7-chloro-3-ethoxycarbonyl-6-(4-phenylpiperidine-1-carbonyl)pyrazolo[1,5-a]pyrimidine (0.15 g, 0.36 mmol) obtained in Example 19, step 4 and 2,2-dimethyl-2,3-dihydro-1-benzofuran-7-amine (0.088 g, 0.54 mmol), the title compound (0.194 g, 99%) was obtained.

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

Procedure: A stirred solution of 10.0 grams (0.061 mole) of 7-amino-2,3-dihydro-2,2-dimethylbenzofuran in 150 mL of N,N-dimethylformamide is cooled in an ice-water bath, and a solution of 10.9 grams (0.061 mole) of N-bromosuccinimide in 50 mL of N,N-dimethylformamide is added in one portion. Upon completion of addition, the reaction mixture is maintained in the ice-water bath for about one hour After this time the reaction mixture is poured into about 600 mL of water. The mixture is then extracted with two 200 mL portions of diethyl ether. The combined extracts are washed with two 100 mL portions of an aqueous 10% lithium chloride solution. The organic layer is dried with magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure, yielding 12.3 grams of 7-amino-4-bromo-2,3-dihydro-2,2-dimethylbenzofuran. The NMR spectrum is consistent with the proposed structure. Upon completion of addition The mixture is then extracted with two 200 mL portions of diethyl ether The combined extracts are washed with two 100 mL portions of an aqueous 10% lithium chloride solution The organic layer is dried with magnesium sulfate filtered The filtrate is concentrated under reduced pressure

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under a nitrogen atmosphere, 10.0 grams (0.061 mole) of 7-amino-2,3-dihydro-2,2-dimethylbenzofuran was stirred and cooled in an ice-water bath. To this was added 17.4 mL (0.153 mole) of aqueous 48% hydrobromic acid, followed by the dropwise addition of a solution of 4.2 grams (0.061 mole) of sodium nitrite in 50 mL of water. The reaction mixture temperature was maintained at below 10° C. throughout the addition. In a separate reaction vessel, a stirred mixture of 4.8 grams (0.034 mole) of copper(I) bromide and 4.2 mL (0.037 mole) of aqueous 48% hydrobromic acid was heated to 60°-70° C., and the diazonium salt prepared above was added slowly dropwise. Upon completion of addition, the reaction mixture was warmed to 80° C. where it was stirred for one hour. After this time the reaction mixture was allowed to cool to ambient temperature as it stirred for about 18 hours. The reaction mixture was poured into 300 mL of water and the mixture was extracted with two 200 mL portions of diethyl ether. The combined extracts were dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residual oil. The oil was subjected to column chromatography on silica gel. Elution was accomplished using petroleum ether. The product-containing fractions were combined and concentrated under reduced pressure, yielding 7.0 grams of 7-bromo-2,3-dihydro-2,2-dimethylbenzofuran. The NMR spectrum was consistent with the proposed structure. cooled in an ice-water bath The reaction mixture temperature was maintained at below 10° C. throughout the addition In a separate reaction vessel was heated to 60°-70° C. above was added slowly dropwise Upon completion of addition to cool to ambient temperature as it stirred for about 18 hours the mixture was extracted with two 200 mL portions of diethyl ether The combined extracts were dried with magnesium sulfate filtered The filtrate was concentrated under reduced pressure to a residual oil Elution concentrated under reduced pressure

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under a nitrogen atmosphere, 10.0 grams (0.061 mole) of 7-amino-2,3-dihydro-2,2-dimethylbenzofuran was stirred and cooled in an ice-water bath. To this was added 17.4 mL (0.153 mole) of aqueous 48% hydrobromic acid, followed by the dropwise addition of a solution of 4.2 grams (0.061 mole) of sodium nitrite in 50 mL of water. The reaction mixture temperature was maintained at below 10° C. throughout the addition. In a separate reaction vessel, a stirred mixture of 4.8 grams (0.034 mole) of copper(I) bromide and 4.2 mL (0.037 mole) of aqueous 48% hydrobromic acid was heated to 60°-70° C., and the diazonium salt prepared above was added slowly dropwise. Upon completion of addition, the reaction mixture was warmed to 80° C. where it was stirred for one hour. After this time the reaction mixture was allowed to cool to ambient temperature as it stirred for about 18 hours. The reaction mixture was poured into 300 mL of water and the mixture was extracted with two 200 mL portions of diethyl ether. The combined extracts were dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residual oil. The oil was subjected to column chromatography on silica gel. Elution was accomplished using petroleum ether. The product-containing fractions were combined and concentrated under reduced pressure, yielding 7.0 grams of 7-bromo-2,3-dihydro-2,2-dimethylbenzofuran. The NMR spectrum was consistent with the proposed structure. cooled in an ice-water bath The reaction mixture temperature was maintained at below 10° C. throughout the addition In a separate reaction vessel was heated to 60°-70° C. above was added slowly dropwise Upon completion of addition to cool to ambient temperature as it stirred for about 18 hours the mixture was extracted with two 200 mL portions of diethyl ether The combined extracts were dried with magnesium sulfate filtered The filtrate was concentrated under reduced pressure to a residual oil Elution concentrated under reduced pressure

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

Procedure: A stirred solution of 10.0 grams (0.061 mole) of 7-amino-2,3-dihydro-2,2-dimethylbenzofuran in 150 mL of N,N-dimethylformamide was cooled in an ice-water bath, and asolution of 10.9 grams (0.061 mole) of N-bromosuccinimide in 50 mL of N,N-dimethylformamide was added in one portion. Upon completion of addition, the reaction mixture was maintained in the ice-water bath for about one hour. After this time the reaction mixture was poured into about 600 mL of water. The mixture was then extracted with two 200 mL portions of diethyl ether. The combined extracts were washed with two 100 mL portions of an aqueous 10% lithium chloride solution. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, yielding 12.3 grams of 7-amino-4-bromo-2,3-dihydro-2,2-dimethylbenzofuran. The NMR spectrum was consistent with the proposed structure. Upon completion of addition The mixture was then extracted with two 200 mL portions of diethyl ether The combined extracts were washed with two 100 mL portions of an aqueous 10% lithium chloride solution The organic layer was dried with magnesium sulfate filtered The filtrate was concentrated under reduced pressure

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

Procedure: A diazonium salt was prepared by adding 13.8 g of sodium nitrite to a suspension of 32.6 g of 7-amino-2,3-dihydro-2,2-dimethylbenzofuran and 40 ml of concentrated sulfuric acid in 200 ml water cooled 0° to 5° C. After stirring for about 0.4 hour at 0° to 5° C., the diazonium salt suspension was poured in one portion into a mixture consisting of 170 ml of acetic acid, 40 ml of concentrated hydrochloric acid, 17 g of cupric chloride dihydrate and 30 ml of sulfur dioxide and cooled by 10° C. by an ice-water bath. The mixture was stirred about 1 hour at 15° to 25° C. Then 400 ml of 1-chlorobutane and 200 ml of water was added and the mixture was stirred and heated at 35° C. for 5 hours. After cooling to room temperature, the organic layer was separated, washed with saturated aqueous NaHCO3 and water, and dried over sodium sulfate for 0.5 hour. The solvent was evaporated under reduced pressure at less than 45° C. to give 26 g of crude 2,3-dihydro-2,2-dimethyl-7-benzofuransulfonyl chloride as an oil. cooled 0° to 5° C The mixture was stirred about 1 hour at 15° to 25° C the mixture was stirred heated at 35° C. for 5 hours After cooling to room temperature the organic layer was separated washed with saturated aqueous NaHCO3 and water dried over sodium sulfate for 0.5 hour The solvent was evaporated under reduced pressure at less than 45° C.