prop-2-ynylsulfanylbenzene

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

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

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

Procedure: The title compound was prepared from prop-2-ynylsulfanyl-benzene and ethyl chloroformate in accordance with the procedures of G. Cai et al., Tetrahedron, 2006, (5697-5708).

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

Procedure: To a flame-dried flask under a nitrogen atmosphere is added N-(4-chlorobenzyl)-4-hydroxy-8-iodo-6-(4-morpholinylmethyl)-3-quinolinecarboxamide (269 mg) of Preparation 26, PdCl2(PPh3)2 (35 mg), and Cu (12 mg). The flask is back-filled with nitrogen gas and charged with dichloromethane (5 mL), Et3N (0.15 mL), and phenyl propargyl sulfide (0.082 mL). The reaction is stirred at room temperature for 7 days. The reaction mixture is diluted with dichloromethane and partitioned against dilute aqueous sodium bicarbonate. The aqueous. phase is extracted with two portions of dichloromethane. The combined organic layers are washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The residue is adsorbed onto silica and flash column chromatographed eluting with 1% to 3% methanol in ethyl acetate. Product containing fractions are combined and condensed to afford a mixture of cyclized and uncyclized materials. To a flask is added the mixture, EtOH (2 mL), and Et3N (0.12 mL). The suspension is heated at 75° C. overnight tightly capped. The reaction mixture is cooled to room temperature, concentrated under reduced pressure, adsorbed onto silica, and flash column chromatographed eluting with 1% to 4% methanol in ethyl acetate. Product-containing fractions are combined and concentrated under reduced pressure to afford a solid. The solid is crystallized from acetonitrile to give 0.16 g of the title compound as light tan product. To a flame-dried flask under a nitrogen atmosphere is added The flask is back-filled with nitrogen gas partitioned against dilute aqueous sodium bicarbonate phase is extracted with two portions of dichloromethane The combined organic layers are washed with brine dried over sodium sulfate concentrated under reduced pressure chromatographed eluting with 1% to 3% methanol in ethyl acetate Product containing fractions condensed to afford a mixture of cyclized and uncyclized materials The suspension is heated at 75° C. overnight tightly capped The reaction mixture is cooled to room temperature concentrated under reduced pressure chromatographed eluting with 1% to 4% methanol in ethyl acetate concentrated under reduced pressure to afford a solid The solid is crystallized from acetonitrile

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

Procedure: The title compound was prepared from prop-2-ynylsulfanyl-benzene and ethyl chloroformate in accordance with the procedures of G. Cai et al., Tetrahedron, 2006, (5697-5708).

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

Procedure: To a flame-dried flask under a nitrogen atmosphere is added N-(4-chlorobenzyl)-4-hydroxy-8-iodo-6-(4-morpholinylmethyl)-3-quinolinecarboxamide (269 mg) of Preparation 26, PdCl2(PPh3)2 (35 mg), and CuI (12 mg). The flask is back-filled with nitrogen gas and charged with dichloromethane (5 mL), Et3N (0.15 mL), and phenyl propargyl sulfide (0.082 mL). The reaction is stirred at room temperature for 7 days. The reaction mixture is diluted with dichloromethane and partitioned against dilute aqueous sodium bicarbonate. The aqueous phase is extracted with two portions of dichloromethane. The combined organic layers are washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The residue is adsorbed onto silica and flash column chromatographed eluting with 1% to 3% methanol in ethyl acetate. Product containing fractions are combined and condensed to afford a mixture of cyclized and uncyclized materials. To a flask is added the mixture, EtOH (2 mL), and Et3N (0.12 mL). The suspension is heated at 75° C. overnight tightly capped. The reaction mixture is cooled to room temperature, concentrated under reduced pressure, adsorbed onto silica, and flash column chromatographed eluting with 1% to 4% methanol in ethyl acetate. Product-containing fractions are combined and concentrated under reduced pressure to afford a solid. The solid is crystallized from acetonitrile to give 0.16 g of the title compound as light tan product. To a flame-dried flask under a nitrogen atmosphere is added The flask is back-filled with nitrogen gas partitioned against dilute aqueous sodium bicarbonate The aqueous phase is extracted with two portions of dichloromethane The combined organic layers are washed with brine dried over sodium sulfate concentrated under reduced pressure chromatographed eluting with 1% to 3% methanol in ethyl acetate Product containing fractions condensed to afford a mixture of cyclized and uncyclized materials The suspension is heated at 75° C. overnight tightly capped The reaction mixture is cooled to room temperature concentrated under reduced pressure chromatographed eluting with 1% to 4% methanol in ethyl acetate concentrated under reduced pressure to afford a solid The solid is crystallized from acetonitrile

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

Procedure: 24.64 ml (12.48 g, 0.0936 mol) of a 3.8N solution of ethylmagnesium bromide in ether was added dropwise, under argon to a cold solution of 13.2 g (0.089 mol) of 3-phenylthio-1-propyne (G. Pourcelot et al, vide supra) in 70 ml of anhydrous tetrahydrofuran. The temperature was maintained at 0°-5° C. Thereafter, the reaction mixture was stirred for 1 hour further at room temperature. Then, 440 mg of cuprous cyanide were added and the solution stirred for 20 minutes more. Then a solution of 7 g (0.0445 mol) of 1-bromo-2,5-hexadiyne in 20 ml of anhydrous tetrahydrofuran was added dropwise, maintaining the temperature between 0°-5° C. After the addition, the reaction mixture was stirred at room temperature for 3 additional hours, and then quenched with 150 ml of 1N sulfuric acid and ice. After extraction with ether (3×150 ml) the combined organic extracts were concentrated in vacuo to a small volume, and washed several times with EDTA and then with water,dried over sodium sulfate and evaporated. The crude material was purified by column chromatography on 150 g of silica gel, using hexane as eluant, to produce 9-phenylthio-1,4,7-nonatriyne, as an oil. The product was stored in dry ice. The temperature was maintained at 0°-5° C the solution stirred for 20 minutes more maintaining the temperature between 0°-5° C After the addition the reaction mixture was stirred at room temperature for 3 additional hours quenched with 150 ml of 1N sulfuric acid and ice After extraction with ether (3×150 ml) the combined organic extracts were concentrated in vacuo to a small volume washed several times with EDTA with water,dried over sodium sulfate and evaporated The crude material was purified by column chromatography on 150 g of silica gel

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

Procedure: To a flame-dried flask under a nitrogen atmosphere is added N-(4-chlorobenzyl)-4-hydroxy-8-iodo-6-(4-morpholinylmethyl)-3-quinolinecarboxamide (269 mg) of Preparation 26, PdCl2(PPh3)2 (35 mg), and Cu (12 mg). The flask is back-filled with nitrogen gas and charged with dichloromethane (5 mL), Et3N (0.15 mL), and phenyl propargyl sulfide (0.082 mL). The reaction is stirred at room temperature for 7 days. The reaction mixture is diluted with dichloromethane and partitioned against dilute aqueous sodium bicarbonate. The aqueous. phase is extracted with two portions of dichloromethane. The combined organic layers are washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The residue is adsorbed onto silica and flash column chromatographed eluting with 1% to 3% methanol in ethyl acetate. Product containing fractions are combined and condensed to afford a mixture of cyclized and uncyclized materials. To a flask is added the mixture, EtOH (2 mL), and Et3N (0.12 mL). The suspension is heated at 75° C. overnight tightly capped. The reaction mixture is cooled to room temperature, concentrated under reduced pressure, adsorbed onto silica, and flash column chromatographed eluting with 1% to 4% methanol in ethyl acetate. Product-containing fractions are combined and concentrated under reduced pressure to afford a solid. The solid is crystallized from acetonitrile to give 0.16 g of the title compound as light tan product. To a flame-dried flask under a nitrogen atmosphere is added The flask is back-filled with nitrogen gas partitioned against dilute aqueous sodium bicarbonate phase is extracted with two portions of dichloromethane The combined organic layers are washed with brine dried over sodium sulfate concentrated under reduced pressure chromatographed eluting with 1% to 3% methanol in ethyl acetate Product containing fractions condensed to afford a mixture of cyclized and uncyclized materials The suspension is heated at 75° C. overnight tightly capped The reaction mixture is cooled to room temperature concentrated under reduced pressure chromatographed eluting with 1% to 4% methanol in ethyl acetate concentrated under reduced pressure to afford a solid The solid is crystallized from acetonitrile

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

Procedure: The title compound was prepared from prop-2-ynylsulfanyl-benzene and ethyl chloroformate in accordance with the procedures of G. Cai et al., Tetrahedron, 2006, (5697-5708).