4-(bromomethyl)-2,2-dimethyloxane

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

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

Procedure: A mixture of 2-butoxy-8-methoxy-9H-purin-6-amine trifluoroacetate salt (223 mg) and potassium carbonate (264 mg) in dry DMF (2 mL) were heated at 60° C. under nitrogen with stirring for 1 h. 4-(Bromomethyl)-2,2-dimethyltetrahydro-2H-pyran (158 mg) was added and the reaction was stirred for 16 h at 60° C. The mixture was quenched with water and extracted with EtOAc (×3). The combined organics were washed with water and brine, dried using a hydrophobic frit and evaporated to give a brown oil. The crude material was purified by normal phase chromatography (ISCO) using 5-20% methanol/EtOAc as eluent to give a pale oil (181 mg). The material was re-purified by normal phase chromatography (ISCO) using 0-15% methanol/EtOAc as eluent to give the title compound (161 mg). the reaction was stirred for 16 h at 60° C The mixture was quenched with water extracted with EtOAc (×3) The combined organics were washed with water and brine dried evaporated to give a brown oil The crude material was purified by normal phase chromatography (ISCO)

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

Procedure: A mixture of (2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl methanesulfonate (1.5 g) and anhydrous lithium bromide (2.72 g) in acetone (40 mL) was refluxed under nitrogen for 4 h. The reaction was allowed to cool and the solvent was evaporated. The residue was treated with saturated sodium bicarbonate solution and was extracted with DCM (×3). The combined organics were washed with dilute brine, dried by passing through a hydrophobic frit and evaporated to give the title compound as a brown oil (1.23 g). was refluxed under nitrogen for 4 h to cool the solvent was evaporated The residue was treated with saturated sodium bicarbonate solution was extracted with DCM (×3) The combined organics were washed with dilute brine dried evaporated

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

Procedure: To a solution of methyl 6-(2-fluoro-5-methoxyphenyl)-5-hydroxynicotinate (739 mg) and 4-(bromomethyl)-2,2-dimethyltetrahydro-2H-pyran (828 mg) in DMF (20 mL) was added potassium carbonate (736 mg), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was poured into water (100 mL), and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/petroleum ether) to give the title compound (950 mg) as a colorless oil. the mixture was extracted with ethyl acetate The extract was dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (ethyl acetate/petroleum ether)

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

Procedure: To a solution of (2,2-dimethyltetrahydro-2H-pyran-4-yl)methanol (2.50 g) in dichloromethane (30 mL) were added carbon tetrabromide (6.80 g) and triphenylphosphine (5.40 g), and the mixture was stirred at room temperature for 20 hr. Water was added and the mixture was extracted with diethyl ether. The extract was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether) to give the title compound (1.10 g) as a colorless oil. the mixture was extracted with diethyl ether The extract was dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (petroleum ether)

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

Procedure: To a solution of (2,2-dimethyltetrahydro-2H-pyran-4-yl)methanol (2.50 g) in dichloromethane (30 mL) were added carbon tetrabromide (6.80 g) and triphenylphosphine (5.40 g), and the mixture was stirred at room temperature for 20 hr. Water was added and the mixture was extracted with diethyl ether. The extract was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether) to give the title compound (1.10 g) as a colorless oil. the mixture was extracted with diethyl ether The extract was dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (petroleum ether)

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

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

Procedure: A mixture of 2-butoxy-8-methoxy-9H-purin-6-amine trifluoroacetate salt (223 mg) and potassium carbonate (264 mg) in dry DMF (2 mL) were heated at 60° C. under nitrogen with stirring for 1 h. 4-(Bromomethyl)-2,2-dimethyltetrahydro-2H-pyran (158 mg) was added and the reaction was stirred for 16 h at 60° C. The mixture was quenched with water and extracted with EtOAc (×3). The combined organics were washed with water and brine, dried using a hydrophobic frit and evaporated to give a brown oil. The crude material was purified by normal phase chromatography (ISCO) using 5-20% methanol/EtOAc as eluent to give a pale oil (181 mg). The material was re-purified by normal phase chromatography (ISCO) using 0-15% methanol/EtOAc as eluent to give the title compound (161 mg). the reaction was stirred for 16 h at 60° C The mixture was quenched with water extracted with EtOAc (×3) The combined organics were washed with water and brine dried evaporated to give a brown oil The crude material was purified by normal phase chromatography (ISCO)

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

Procedure: A mixture of (2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl methanesulfonate (1.5 g) and anhydrous lithium bromide (2.72 g) in acetone (40 mL) was refluxed under nitrogen for 4 h. The reaction was allowed to cool and the solvent was evaporated. The residue was treated with saturated sodium bicarbonate solution and was extracted with DCM (×3). The combined organics were washed with dilute brine, dried by passing through a hydrophobic frit and evaporated to give the title compound as a brown oil (1.23 g). was refluxed under nitrogen for 4 h to cool the solvent was evaporated The residue was treated with saturated sodium bicarbonate solution was extracted with DCM (×3) The combined organics were washed with dilute brine dried evaporated

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

Procedure: To a solution of methyl 6-(2-fluoro-5-methoxyphenyl)-5-hydroxynicotinate (739 mg) and 4-(bromomethyl)-2,2-dimethyltetrahydro-2H-pyran (828 mg) in DMF (20 mL) was added potassium carbonate (736 mg), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was poured into water (100 mL), and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/petroleum ether) to give the title compound (950 mg) as a colorless oil. the mixture was extracted with ethyl acetate The extract was dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (ethyl acetate/petroleum ether)

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

Procedure: To a solution of (2,2-dimethyltetrahydro-2H-pyran-4-yl)methanol (2.50 g) in dichloromethane (30 mL) were added carbon tetrabromide (6.80 g) and triphenylphosphine (5.40 g), and the mixture was stirred at room temperature for 20 hr. Water was added and the mixture was extracted with diethyl ether. The extract was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether) to give the title compound (1.10 g) as a colorless oil. the mixture was extracted with diethyl ether The extract was dried over anhydrous sodium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (petroleum ether)