2-methylpropylboronic acid

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

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under an argon gas atmosphere, 2-bromo-5-nitrobenzonitrile (2.0 g), isobutylboronic acid (988 mg), cesium carbonate (5.7 g), and PdCl2 (dppf)-CH2Cl2 (720 mg) were dissolved in toluene (25 ml) and water (1 ml). The mixture was stirred at 100° C. for 18 hours. After the mixture was cooled to room temperature, the mixture was diluted with diethyl ether and water followed by the step of extraction/separation. The organic layer was washed with 1 N-hydrochloric acid, 5 N-sodium hydroxide aqueous solution and saturated brine, and dried over anhydrous magnesium sulfate. After the solvent was evaporated under reduced pressure, the resulting residue was purified on column chromatography (EtOAc:hexane=1:3) to obtain the title compound (1.06 g) as a pale yellow oily substance. After the mixture was cooled to room temperature followed by the step of extraction/separation The organic layer was washed with 1 N-hydrochloric acid, 5 N-sodium hydroxide aqueous solution and saturated brine dried over anhydrous magnesium sulfate After the solvent was evaporated under reduced pressure the resulting residue was purified on column chromatography (EtOAc:hexane=1:3)

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

Procedure: A mixture of 4-Benzyloxy-1-bromo-isoquinoline-3-carboxylic acid butyl ester (207 mg, 0.5 mmol, see example D-86 a), Pd(PPh3)4 (58 mg, 0.05 mmol), 2-methylpropylboronic acid (78 mg, 0.75 mmol), K2CO3 (207 mg, 1.5 mmol), and 1,4-dioxane (4 ml) was refluxed with stirring for 48 h. Subsequently, the mixture was concentrated in vacuo. To the residue was added water (5 ml) and the mixture was extracted with EtOAc (2×20 ml). The organic phase was dried over MgSO4 and evaporated in vacuo. Purification of the residue by flash column chromatography on silica gel using hexanes EtOAc=88 12 as the eluent gave the title compound as a yellowish oil (136 mg); MS-(+)-ion M+1=392.3. Subsequently, the mixture was concentrated in vacuo To the residue was added water (5 ml) the mixture was extracted with EtOAc (2×20 ml) The organic phase was dried over MgSO4 evaporated in vacuo Purification of the residue by flash column chromatography on silica gel

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

Procedure: A mixture of 4-Benzyloxy-1-bromo-isoquinoline-3-carboxylic acid butyl ester (207 mg, 0.5 mmol, see example D-86 a), Pd(PPh3)4 (58 mg, 0.05 mmol), 2-methylpropylboronic acid (78 mg, 0.75 mmol), K2CO3 (207 mg, 1.5 mmol), and 1,4-dioxane (4 ml) was refluxed with stirring for 48 h. Subsequently, the mixture was concentrated in vacuo. To the residue was added water (5 ml) and the mixture was extracted with EtOAc (2×20 ml). The organic phase was dried over MgSO4 and evaporated in vacuo. Purification of the residue by flash column chromatography on silica gel using hexanes EtOAc=88 12 as the eluent gave the title compound as a yellowish oil (136 mg); MS-(+)-ion M+1=392.3. Subsequently, the mixture was concentrated in vacuo To the residue was added water (5 ml) the mixture was extracted with EtOAc (2×20 ml) The organic phase was dried over MgSO4 evaporated in vacuo Purification of the residue by flash column chromatography on silica gel

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

Procedure: A mixture of (+)-pinanediol (23.9 g, 0.140 mol) and 2-methylpropylboronic acid (15 g, 0.147 mol) in diethyl ether (300 ml) was stirred at room temperature for 24 h. The mixture was dried over anhydrous sodium sulfate and purified by column chromatography (Silica gel 230-400 mesh), eluting with hexane:ethyl acetate 90:10 mixture. The product was obtained as a clear oil (32.6 g, 94% yield). The mixture was dried over anhydrous sodium sulfate purified by column chromatography (Silica gel 230-400 mesh) eluting with hexane:ethyl acetate 90:10 mixture

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

Procedure: A mixture of 1,6-dibromopyrene (15.13 g, 42.0 mmol), isobutyl boronic acid (27.58 g, 270 mmol), potassium phosphate tribasic monohydrate (53.94 g, 254 mmol), Pd2(dba)3 (3.02 g, 3.30 mmol), and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (1.00 g, 2.45 mmol) in toluene (300 mL) was fully degassing by bubbling through with nitrogen. The reaction mixture was maintained at reflux under nitrogen for 16 h. The reaction mixture was cooled, then filtered through a pad of Celite and washed with toluene. The solvent was removed in vacuo and the residue was purified by flash chromatography using hexane to yield 1,6-diisobutylpyrene (10.18 g, 77% yield) as a white solid. was fully degassing by bubbling through with nitrogen The reaction mixture was maintained at reflux under nitrogen for 16 h The reaction mixture was cooled filtered through a pad of Celite washed with toluene The solvent was removed in vacuo the residue was purified by flash chromatography

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

Procedure: A mixture of 4-Benzyloxy-1-bromo-isoquinoline-3-carboxylic acid butyl ester (207 mg, 0.5 mmol, see example D-86 a), Pd(PPh3)4 (58 mg, 0.05 mmol), 2-methylpropylboronic acid (78 mg, 0.75 mmol), K2CO3 (207 mg, 1.5 mmol), and 1,4-dioxane (4 ml) was refluxed with stirring for 48 h. Subsequently, the mixture was concentrated in vacuo. To the residue was added water (5 ml) and the mixture was extracted with EtOAc (2×20 ml). The organic phase was dried over MgSO4 and evaporated in vacuo. Purification of the residue by flash column chromatography on silica gel using hexanes EtOAc=88 12 as the eluent gave the title compound as a yellowish oil (136 mg); MS-(+)-ion M+1=392.3. Subsequently, the mixture was concentrated in vacuo To the residue was added water (5 ml) the mixture was extracted with EtOAc (2×20 ml) The organic phase was dried over MgSO4 evaporated in vacuo Purification of the residue by flash column chromatography on silica gel

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of ethyl 6-chloro-3-methylpyrazine-2-carboxylate (1.94 g, 9.67 mmol), isobutylboronic acid (1.97 g, 19.3 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II)(212 mg, 0.290 mmol), and potassium carbonate (2.67 g, 19.3 mmol) in 1,4-dioxane (30 mL) was heated at 100° C. for 4.5 h. After being cooled to ambient temperature, the reaction mixture was diluted with ethyl acetate and filtrated through celite with ethyl acetate. The filtrate was combined and concentrated in vacuo. The residue was diluted ethyl acetate, and washed with saturated aqueous sodium bicarbonate and saturated brine, dried over sodium bicarbonate, filtrated and concentrated in vacuo. The residue was dissolved to dichloromethane, and the insoluble materials were filtered off. The filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1 to 3:1) to give ethyl 6-isobutyl-3-methylpyrazine-2-carboxylate. MS (APCI): m/z 223 (M+H). After being cooled to ambient temperature filtrated through celite with ethyl acetate concentrated in vacuo washed with saturated aqueous sodium bicarbonate and saturated brine dried over sodium bicarbonate filtrated concentrated in vacuo The residue was dissolved to dichloromethane the insoluble materials were filtered off The filtrate was concentrated in vacuo The residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1 to 3:1)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of ethyl 6-chloro-3-methylpyrazine-2-carboxylate (1.94 g, 9.67 mmol), isobutylboronic acid (1.97 g, 19.3 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II)(212 mg, 0.290 mmol), and potassium carbonate (2.67 g, 19.3 mmol) in 1,4-dioxane (30 mL) was heated at 100° C. for 4.5 h. After being cooled to ambient temperature, the reaction mixture was diluted with ethyl acetate and filtrated through celite with ethyl acetate. The filtrate was combined and concentrated in vacuo. The residue was diluted ethyl acetate, and washed with saturated aqueous sodium bicarbonate and saturated brine, dried over sodium bicarbonate, filtrated and concentrated in vacuo. The residue was dissolved to dichloromethane, and the insoluble materials were filtered off. The filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1 to 3:1) to give ethyl 6-isobutyl-3-methylpyrazine-2-carboxylate. MS (APCI): m/z 223 (M+H). After being cooled to ambient temperature filtrated through celite with ethyl acetate concentrated in vacuo washed with saturated aqueous sodium bicarbonate and saturated brine dried over sodium bicarbonate filtrated concentrated in vacuo The residue was dissolved to dichloromethane the insoluble materials were filtered off The filtrate was concentrated in vacuo The residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1 to 3:1)

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

Procedure: 8-chloro-2,4-dimethyl-5,6-dihydrobenzo[c]acridine (15.0 g, 51.1 mmol), isobutylboronic acid (7.8 g, 77 mmol), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (1.6 g, 4.08 mmol) potassium phosphate monohydrate (41.2 g, 179 mmol) were mixed in 300 mL of toluene. The system was degassed for 20 minutes. Pd2(dba)3 (0.93 g, 1.02 mmol) was then added and the system was refluxed overnight. After cooling to room temperature, the reaction mixture was filtered through a Celite® plug and eluted with 30% ethyl acetate in toluene. ˜19.5 crude liquid was obtained. The crude product was recrystallized from 5% acetone in hexane to obtain ˜14.9 g pure product (99.6%) which was confirmed by GC-MS. The system was degassed for 20 minutes the system was refluxed overnight the reaction mixture was filtered through a Celite® plug eluted with 30% ethyl acetate in toluene ˜19.5 crude liquid was obtained The crude product was recrystallized from 5% acetone in hexane

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

Procedure: 5-Bromo-2-(dibenzo[b,d]furan-4-yl)-4-methylpyridine (13.0 g, 38.3 mmol), isobutylboronic acid (11.7 g, 115 mmol), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (0.63 g, 1.53 mmol) and potassium phosphate monohydrate (22.1 g, 96 mmol) were mixed in water (10 mL) and toluene (210 mL). The system was degassed for 20 min. with nitrogen and Pd2(dba)3 (0.35 g, 0.38 mmol) was then added and the system was refluxed overnight. After cooling to room temperature, the reaction mixture was filtered through a small plug of silica gel and eluted with dicloromethane. The filtrated was concentrated and then crystallized from hexane to give 2-(dibenzo[b,d]furan-4-yl)-5-isobutyl-4-methylpyridine (9.0 g, 74%). was then added the system was refluxed overnight the reaction mixture was filtered through a small plug of silica gel eluted with dicloromethane The filtrated was concentrated crystallized from hexane

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

Procedure: 5-Bromo-2-(dibenzo[b,d]furan-4-yl)-4-methylpyridine (13.0 g, 38.3 mmol), isobutylboronic acid (11.7 g, 115 mmol), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (0.63 g, 1.53 mmol) and potassium phosphate monohydrate (22.1 g, 96 mmol) were mixed in water (10 mL) and toluene (210 mL). The system was degassed for 20 min. with nitrogen and Pd2(dba)3 (0.35 g, 0.38 mmol) was then added and the system was refluxed overnight. After cooling to room temperature, the reaction mixture was filtered through a small plug of silica gel and eluted with dicloromethane. The filtrated was concentrated and then crystallized from hexane to give 2-(dibenzo[b,d]furan-4-yl)-5-isobutyl-4-methylpyridine (9.0 g, 74%). was then added the system was refluxed overnight the reaction mixture was filtered through a small plug of silica gel eluted with dicloromethane The filtrated was concentrated crystallized from hexane