4-chloro-1-fluoro-2-iodobenzene

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

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

Procedure: A mixture of 5-chloro-2-fluoroiodobenzene (5.00 g), copper(I) iodide (74.3 mg), triphenylphosphine (256 mg), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (404 mg), propargyl alcohol (1.27 ml), diisopropylethylamine (13.6 ml) and tetrahydrofuran (100 ml) was stirred at room temperature for 8 hr. The reaction mixture was added to brine, and the mixture was extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=99:1-80:20) to give the object product (2.82 g) as a brown oil. the mixture was extracted with ethyl acetate washed with saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (hexane:ethyl acetate=99:1-80:20)

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

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

Procedure: A solution of 2-(4-(ethylsulfonyl)-2-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (Preparation 45, 1.77 g, 5.64 mmol), 4-chloro-1-fluoro-2-iodobenzene (1.28 g, 5.00 mmol), and sodium carbonate (1.59 g, 15.00 mmol) in dioxane (40 mL) and water (10 mL) was degassed. Tetrakis(triphenylphosphine)palladium(0) (577 mg, 0.50 mmol) was added and the mixture was degassed twice more, and the reaction warmed to 80° C. for 2 hours. The reaction was cooled and diluted with EtOAc (50 mL) and water (50 mL), the layers separated and the aqueous extracted with EtOAc (2×30 mL). The combined organic layers were washed with brine (30 mL), dried over MgSO4 and the solvent removed in vacuo. The crude was purified by silica gel column chromatography eluting with EtOAc:heptane 1:19 to 1:1 to give the title compound as a colourless oil 28% yield, 443 mg. the mixture was degassed twice more The reaction was cooled diluted with EtOAc (50 mL) and water (50 mL) the layers separated the aqueous extracted with EtOAc (2×30 mL) The combined organic layers were washed with brine (30 mL) dried over MgSO4 the solvent removed in vacuo The crude was purified by silica gel column chromatography eluting with EtOAc:heptane 1:19 to 1:1

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

Procedure: (2,4-Dimethoxy-benzyl)-(2-oxo-1-phenyl-1,2,3,4-tetrahydro-pyrido[3,2-d]pyrimidin-6-yl)-carbamic acid tert-butyl ester (380 mg, 0.77 mmol) was treated according to the procedure of Example 21, Step 1, using 4-chloro-1-fluoro-2-iodo-benzene instead of 1-chloro-4-iodo-benzene to afford [3-(5-chloro-2-fluoro-phenyl)-2-oxo-1-phenyl-1,2,3,4-tetrahydro-pyrido[3,2-d]pyrimidin-6-yl]-(2,4-dimethoxy-benzyl)-carbamic acid tert-butyl ester (233 mg). MS: [M+H]+=619.

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

Procedure: A mixture of 5-chloro-2-fluoroiodobenzene (5.00 g), copper(I) iodide (74.3 mg), triphenylphosphine (256 mg), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (404 mg), propargyl alcohol (1.27 ml), diisopropylethylamine (13.6 ml) and tetrahydrofuran (100 ml) was stirred at room temperature for 8 hr. The reaction mixture was added to brine, and the mixture was extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=99:1-80:20) to give the object product (2.82 g) as a brown oil. the mixture was extracted with ethyl acetate washed with saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (hexane:ethyl acetate=99:1-80:20)

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