trimethyl(2-phenylethynyl)silane

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

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

Procedure: (rac)-rel-{(3aR,4R,6R,6aS)-2,2-dimethyl-6-[(2-{3-[(trimethylsilyl)ethynyl]phenyl}pyrazolo[1,5-a]pyrimidin-7-yl)amino]tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl}methanol (0.067 g, 0.00014 mol; synthesized following Step 1 in Method A except using 4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylethynyl-trimethylsilane instead of 1-naphthaleneboronic acid) is dissolved in methanol (0.03 mL, 0.0007 mol). Potassium carbonate (21 mg, 0.00015 mol) is added and the solution is stirred at room temperature overnight. The reaction mixture is neutralized with saturated ammonium chloride solution and extracted with dichlormethane. The organic layer is concentrated in vacuo and purified by column chromatography (0-15% MeOH/CH2Cl2) to provide (rac)-rel-[(3aR,4R,6R,6aS)-6-{[2-(3-ethynylphenyl)pyrazolo[1,5-a]pyrimidin-7-yl]amino}-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]methanol (0.046 g, yield 81%). LCMS: (AA) M+ 405; 1H NMR (400 MHz, DMSO) δ 8.25-8.05 (m, 4H), 7.52-7.44 (m, 2H), 7.00 (s, 1H), 6.25 (d, J=5.4 Hz, 1H), 5.25-5.17 (m, 1H), 4.59-4.48 (m, 2H), 4.27 (s, 1H), 4.16-3.99 (m, 1H), 3.65-3.44 (m, 2H), 2.48-2.38 (m, 1H), 2.28-2.19 (m, 1H), 1.87-1.72 (m, 1H), 1.46 (s, 3H), 1.24 (s, 3H). extracted with dichlormethane The organic layer is concentrated in vacuo purified by column chromatography (0-15% MeOH/CH2Cl2)

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

Procedure: A solution of iodobenzene (1 mmole) in DMF (5 mL) was treated with trimethylsilylacetylene (2 mmole), Pd(PPh3)2Cl2 (0.035 mmole), CuI (0.08 mmole) and triethylamine (4 mmole), and the resulting reaction mixture was stirred under nitrogen at room temperature for 5 h. Evaporation followed by chromatography gave 1-trimethylsilyl-2-phenylacetylene as a solid. the resulting reaction mixture Evaporation

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

Procedure: A reactor with a capacity of 40 mL, equipped with a magnetic stirrer was filled, under argon atmosphere, with 0.0085 g (0.015 mmol) of [{Ir(μ-Cl)(CO)2}2], and then with 8 mL of anhydrous and deoxidized toluene and 0.7 g (5.4 mmol) of NEt(i-Pr)2. The whole mixture was stirred until the starting iridium(I) complex was dissolved, and then 0.306 g (3mmol) of phenylacetylene and 0.96 g (4.8 mmol) of ISiMe3 were added to the resulting mixture. The reaction was carried out at a temperature of 80° C. until complete conversion of phenylacetylene. After the reaction was completed, the solvent was evaporated at a reduced pressure along with any residual unreacted substrates in order to remove the catalyst from the reaction mixture and then the residue was transferred onto a chromatographic column packed with silica gel and product was isolated using hexane as eluent. The solvent was initially evaporated from the eluate, and the residual product was distilled by means of the “trap-to-trap” technique at a reduced pressure to obtain 0.47 g of phenylethynyltrirnethylsilane, with a yield of 90%. A reactor with a capacity of 40 mL, equipped with a magnetic stirrer was dissolved the solvent was evaporated at a reduced pressure along with any residual unreacted substrates in order to remove the catalyst from the reaction mixture product was isolated The solvent was initially evaporated from the eluate, and the residual product was distilled by means of the “trap-to-trap” technique at a reduced pressure

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

Procedure: A reactor with a capacity of 40 mL, equipped with a magnetic stirrer was filled, under argon atmosphere, with 0.0085 g (0.015 mmol) of [{Ir(μ-Cl)(CO)2}2], and then with 8 mL of anhydrous and deoxidized toluene and 0.7 g (5.4 mmol) of NEt(i-Pr)2. The whole mixture was stirred until the starting iridium(I) complex was dissolved, and then 0.306 g (3mmol) of phenylacetylene and 0.96 g (4.8 mmol) of ISiMe3 were added to the resulting mixture. The reaction was carried out at a temperature of 80° C. until complete conversion of phenylacetylene. After the reaction was completed, the solvent was evaporated at a reduced pressure along with any residual unreacted substrates in order to remove the catalyst from the reaction mixture and then the residue was transferred onto a chromatographic column packed with silica gel and product was isolated using hexane as eluent. The solvent was initially evaporated from the eluate, and the residual product was distilled by means of the “trap-to-trap” technique at a reduced pressure to obtain 0.47 g of phenylethynyltrirnethylsilane, with a yield of 90%. A reactor with a capacity of 40 mL, equipped with a magnetic stirrer was dissolved the solvent was evaporated at a reduced pressure along with any residual unreacted substrates in order to remove the catalyst from the reaction mixture product was isolated The solvent was initially evaporated from the eluate, and the residual product was distilled by means of the “trap-to-trap” technique at a reduced pressure

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

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

Procedure: 2-Amino-5-chloro-3-nitro-phenyliodide (1.5 g, 4.90 mmol) prepared in Preparation 19 and 1-phenyl-2-trimethylsilylacetylene (4.3 g, 24.50 mmol) were dissolved in DMF (50 mL). Palladium acetate (0.11 g, 0.5 mmol), lithium chloride (0.21 g, 4.90 mmol) and triethylamine (2.48 g, 24.50 mmol) were added thereto, and the mixture was stirred under heating for 3 h to 100° C. After completion of the reaction, water was added to the reaction mixture, which was then extracted with ethyl acetate, washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and filtered. The solvent was removed under reduced pressure, and the residue was purified by column chromatography to give the title compound (1.05 g, Yield 87%). under heating for 3 h to 100° C was added to the reaction mixture, which was then extracted with ethyl acetate washed with saturated aqueous sodium chloride solution dried over anhydrous magnesium sulfate filtered The solvent was removed under reduced pressure the residue was purified by column chromatography

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

Procedure: 4-Amino-3-nitro-benzoic acid ethyl ester and trimethyl-phenylethynyl-silane were reacted according to the same procedures as Preparation 19 to give 7-nitro-3-phenyl-2-trimethylsilanyl-1H-indole-5-carboxylic acid ethyl ester. according to the same procedures as Preparation 19

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

Procedure: 2-Amino-5-chloro-3-nitro-phenyliodide (1.5 g, 4.90 mmol) prepared in Preparation 19 and 1-phenyl-2-trimethylsilylacetylene (4.3 g, 24.50 mmol) were dissolved in DMF (50 mL). Palladium acetate (0.11 g, 0.5 mmol), lithium chloride (0.21 g, 4.90 mmol) and triethylamine (2.48 g, 24.50 mmol) were added thereto, and the mixture was stirred under heating for 3 h to 100□. After completion of the reaction, water was added to the reaction mixture, which was then extracted with ethyl acetate, washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and filtered. The solvent was removed under reduced pressure, and the residue was purified by column chromatography to give the title compound (1.05 g, Yield 87%). under heating for 3 h to 100□ was added to the reaction mixture, which was then extracted with ethyl acetate washed with saturated aqueous sodium chloride solution dried over anhydrous magnesium sulfate filtered The solvent was removed under reduced pressure the residue was purified by column chromatography

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

Procedure: (rac)-rel-{(3aR,4R,6R,6aS)-2,2-dimethyl-6-[(2-{3-[(trimethylsilyl)ethynyl]phenyl}pyrazolo[1,5-a]pyrimidin-7-yl)amino]tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl}methanol (0.067 g, 0.00014 mol; synthesized following Step 1 in Method A except using 4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylethynyl-trimethylsilane instead of 1-naphthaleneboronic acid) is dissolved in methanol (0.03 mL, 0.0007 mol). Potassium carbonate (21 mg, 0.00015 mol) is added and the solution is stirred at room temperature overnight. The reaction mixture is neutralized with saturated ammonium chloride solution and extracted with dichlormethane. The organic layer is concentrated in vacuo and purified by column chromatography (0-15% MeOH/CH2Cl2) to provide (rac)-rel-[(3aR,4R,6R,6aS)-6-{[2-(3-ethynylphenyl)pyrazolo[1,5-a]pyrimidin-7-yl]amino}-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]methanol (0.046 g, yield 81%). LCMS: (AA) M+ 405; 1H NMR (400 MHz, DMSO) δ 8.25-8.05 (m, 4H), 7.52-7.44 (m, 2H), 7.00 (s, 1H), 6.25 (d, J=5.4 Hz, 1H), 5.25-5.17 (m, 1H), 4.59-4.48 (m, 2H), 4.27 (s, 1H), 4.16-3.99 (m, 1H), 3.65-3.44 (m, 2H), 2.48-2.38 (m, 1H), 2.28-2.19 (m, 1H), 1.87-1.72 (m, 1H), 1.46 (s, 3H), 1.24 (s, 3H). extracted with dichlormethane The organic layer is concentrated in vacuo purified by column chromatography (0-15% MeOH/CH2Cl2)

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

Procedure: A resealable tube was charged with 1-benzyl-4-benzyloxy-3-iodo-2-pyridone 3 (5.000 g, 11.98 mmol), acetonitrile (100 mL), and triethylamine (6.06 g, 8.35 mL, 59.9 mmol). Dichlorobis(triphenylphosphine)palladium (II) (0.841 g, 1.20 mmol) and 1-phenyl-2-(trimethylsilyl)acetylene were added and argon was bubbled through the solution. The tube was sealed and the mixture stirred at 100° C. for 4 h. The reaction mixture was concentrated to afford 7-benzyl-3-phenyl-2-(trimethylsilyl)furo[2,3-b]pyridin-4(7H)-one 4d as a brown oil. MS (MH+) 374.2; Calculated 373 for C23H23NO2Si. argon was bubbled through the solution The tube was sealed The reaction mixture was concentrated

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

Procedure: A solution of iodobenzene (1 mmole) in DME (5 mL) was treated with trimethylsilylacetylene (2 mmole), Pd(PPh3)2Cl2 (0.035 mmole), CuI (0.08 mmole) and triethylamine (4 mmole), and the resulting reaction mixture was stirred under nitrogen at room temperature for 5 h. Evaporation followed by chromatography gave 1-trimethylsilyl-2-phenylacetylene as a solid. the resulting reaction mixture Evaporation