3-trimethylsilylprop-2-yn-1-ol

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

Procedure: A solution of 2-azido-1,3-dichloro-benzene (4.00 g, 1 equiv) and 3-trimethylsilanyl-prop-2-yn-1-ol (6.29 mL, 2 equiv) in toluene (10 mL) is heated to 120° C. for 23 h. The reaction mixture is allowed to cool to room temperature and is diluted with 100 mL methylene chloride. The solution is adsorbed onto diatomaceous earth and is purified via flash chromatography eluting with hexanes/ethyl acetate (85:15 to 20:80) to give [3-(2,6-Dichloro-phenyl)-3H-[1,2,3]triazol-4-yl]-methanol (2.30 g, 44%) as an off-white solid. is purified via flash chromatography eluting with hexanes/ethyl acetate (85:15 to 20:80)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 50 mL round bottom flask was charged with dihydropyran, (3.5 mL, 39 mmol) and pTSA, (7 mg, 0.039 mmol) was added. When the pTSA had dissolved, the solution was cooled to 0° C. in an ice bath and 3-(trimethylsilyl)propargyl alcohol, (5.7 mL, 39 mmol) was added dropwise. It was allowed then allowed to warm slowly to room temperature and held for 1 h. The mixture was added to saturated NaHCO3, (250 mL) extracted with Et2O, (150 mL) (×3), washed with brine, (150 mL), dried (Na2SO4) and the solvent was evaporated under reduced pressure. The material was purified by chromatography eluting with heptane-EtOAc, gradient 0 to 10% EtOAc. 8.5 g. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.19 (s, 9H) 0.77-0.94 (m, 1H) 1.49-1.59 (m, 1H) 1.57-1.70 (m, 2H) 1.69-1.93 (m, 2H) 3.35-3.63 (m, 1H) 3.78-3.91 (m, 1H) 4.19-4.35 (m, 2H) 4.82 (t, J=3.34 Hz, 1H). was added to warm slowly to room temperature extracted with Et2O, (150 mL) (×3) washed with brine, (150 mL) dried (Na2SO4) the solvent was evaporated under reduced pressure The material was purified by chromatography eluting with heptane-EtOAc, gradient 0 to 10% EtOAc

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

Procedure: A solution of 2-azido-1,3-dichloro-benzene (4.00 g, 1 equiv) and 3-trimethylsilanyl-prop-2-yn-1-ol (6.29 mL, 2 equiv) in toluene (10 mL) is heated to 120° C. for 23 h. The reaction mixture is allowed to cool to room temperature and is diluted with 100 mL methylene chloride. The solution is adsorbed onto diatomaceous earth and is purified via flash chromatography eluting with hexanes/ethyl acetate (85:15 to 20:80) to give [3-(2,6-Dichloro-phenyl)-3H-[1,2,3]triazol-4-yl]-methanol (2.30 g, 44%) as an off-white solid. is purified via flash chromatography eluting with hexanes/ethyl acetate (85:15 to 20:80)

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

Procedure: A solution of 2-azido-1,3-dichloro-benzene (4.00 g, 1 equiv) and 3-trimethylsilanyl-prop-2-yn-1-ol (6.29 mL, 2 equiv) in toluene (10 mL) is heated to 120° C. for 23 h. The reaction mixture is allowed to cool to room temperature and is diluted with 100 mL methylene chloride. The solution is adsorbed onto diatomaceous earth and is purified via flash chromatography eluting with hexanes/ethyl acetate (85:15 to 20:80) to give [3-(2,6-Dichloro-phenyl)-3H-[1,2,3]triazol-4-yl]-methanol (2.30 g, 44%) as an off-white solid. is purified via flash chromatography eluting with hexanes/ethyl acetate (85:15 to 20:80)

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

Procedure: Under an argon atmosphere 44 mg (0.34 mmol) 3-trimethylsilanyl-prop-2-yn-1-ol, 50 μL TEA, 13 mg 1,1′-bis(diphenylphosphine)ferrocene dichloropalladium (II) and 3 mg (20 μmol) copper(I) iodide were added to 0.10 g (0.17 mmol) 1-[2′-(5-fluoro-2,3-dihydro-indole-1-carbonyl)-5′-iodo-3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-4-yl]-1,3-dihydro-imidazo[4,5-b]pyridin-2-one in 4.0 mL 1,4-dioxane. Then 0.36 mL (0.36 mmol) of a 1 molar tetrabutylammonium fluoride solution in THF were added dropwise and the mixture was then stirred for 4 h at 80° C. The reaction mixture was mixed with water and the precipitate formed was suction filtered. The precipitate was stirred in 6 mL DMF and suction filtered. The filtrate was purified by preparative HPLC-MS. The product-containing fractions were combined and freeze-dried. the precipitate formed filtered The precipitate was stirred in 6 mL DMF suction filtered The filtrate was purified by preparative HPLC-MS freeze-dried

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 50 mL round bottom flask was charged with dihydropyran, (3.5 mL, 39 mmol) and pTSA, (7 mg, 0.039 mmol) was added. When the pTSA had dissolved, the solution was cooled to 0° C. in an ice bath and 3-(trimethylsilyl)propargyl alcohol, (5.7 mL, 39 mmol) was added dropwise. It was allowed then allowed to warm slowly to room temperature and held for 1 h. The mixture was added to saturated NaHCO3, (250 mL) extracted with Et2O, (150 mL) (×3), washed with brine, (150 mL), dried (Na2SO4) and the solvent was evaporated under reduced pressure. The material was purified by chromatography eluting with heptane-EtOAc, gradient 0 to 10% EtOAc. 8.5 g. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.19 (s, 9H) 0.77-0.94 (m, 1H) 1.49-1.59 (m, 1H) 1.57-1.70 (m, 2H) 1.69-1.93 (m, 2H) 3.35-3.63 (m, 1H) 3.78-3.91 (m, 1H) 4.19-4.35 (m, 2H) 4.82 (t, J=3.34 Hz, 1H). was added to warm slowly to room temperature extracted with Et2O, (150 mL) (×3) washed with brine, (150 mL) dried (Na2SO4) the solvent was evaporated under reduced pressure The material was purified by chromatography eluting with heptane-EtOAc, gradient 0 to 10% EtOAc

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

Procedure: A solution of 2-azido-1,3-dichloro-benzene (4.00 g, 1 equiv) and 3-trimethylsilanyl-prop-2-yn-1-ol (6.29 mL, 2 equiv) in toluene (10 mL) is heated to 120° C. for 23 h. The reaction mixture is allowed to cool to room temperature and is diluted with 100 mL methylene chloride. The solution is adsorbed onto diatomaceous earth and is purified via flash chromatography eluting with hexanes/ethyl acetate (85:15 to 20:80) to give [3-(2,6-Dichloro-phenyl)-3H-[1,2,3]triazol-4-yl]-methanol (2.30 g, 44%) as an off-white solid. is purified via flash chromatography eluting with hexanes/ethyl acetate (85:15 to 20:80)