1-prop-2-ynylimidazolidin-2-one

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

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: Chloroetyl isocyanate (12.2 g, 0.11 mol) was added at 0° C. to a stirred solution of propargylamine (6.6 g, 0.12 mol) in THF (200 mL). The solution was allowed to warm to room temperature and sodium hydride (5.5 g of 50% in oil, washed with ether to remove the oil) was added. The reaction was quenched with acetic acid (6.0 mL), the THF was removed under reduced pressure, and the residue was partitioned between ethyl acetate and water. The ethyl acetate was evaporated and the residual solid was crystallized from ethyl acetate:Skellysolve B to give 11.1 g of 1-(2-propynyl)-2-imidazolidinone, m.p. 110°-115° C. sodium hydride (5.5 g of 50% in oil, washed with ether to remove the oil) was added The reaction was quenched with acetic acid (6.0 mL) the THF was removed under reduced pressure the residue was partitioned between ethyl acetate and water The ethyl acetate was evaporated the residual solid was crystallized from ethyl acetate

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

Procedure: Chloroethyl isocyanate (12.2 g, 0.11 mol) was added at 0° C. to a stirred solution of propargylamine (6.6 g, 0.12 mol) in THF (200 mL). The solution was allowed to warm to room temperature and sodium hydride (5.5 g of 50% in oil, washed with ether to remove the oil) was added. The reaction was quenched with acetic acid (6.0 mL), the THF was removed under reduced pressure, and the residue was partitioned between ethyl acetate and water. The ethyl acetate was evaporated and the residual solid was crystallized from ethyl acetate: Skellysolve B to give 11.1 g of 1-(2-propynyl)-2-imidazolidinone, m.p. 110°-115° C. sodium hydride (5.5 g of 50% in oil, washed with ether to remove the oil) was added The reaction was quenched with acetic acid (6.0 mL) the THF was removed under reduced pressure the residue was partitioned between ethyl acetate and water The ethyl acetate was evaporated the residual solid was crystallized from ethyl acetate

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

Procedure: Chloroethyl isocyanate (12.2 g, 0.11 mol) was added at 0° C. to a stirred solution of propargylamine (6.6 g, 0.12 mol) in THF (200 mL). The solution was allowed to warm to room temperature and sodium hydride (5.5 g of 50% in oil, washed with ether to remove the oil) was added. The reaction was quenched with acetic acid (6.0 mL), the THF was removed under reduced pressure, and the residue was partitioned between ethyl acetate and water. The ethyl acetate was evaporated and the residual solid was crystallized from ethyl acetate: Skellysolve B to give 11.1 g of 1-(2-propynyl)-2-imidazolidinone, m.p. 110°-115° C. sodium hydride (5.5 g of 50% in oil, washed with ether to remove the oil) was added The reaction was quenched with acetic acid (6.0 mL) the THF was removed under reduced pressure the residue was partitioned between ethyl acetate and water The ethyl acetate was evaporated the residual solid was crystallized from ethyl acetate

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

Procedure: Chloroethyl isocyanate (12.2 g, 0.11 mol) was added at 0° C. to a stirred solution of propargylamine (6.6 g, 0.12 mol) in THF (200 mL). The solution was allowed to warm to room temperature and sodium hydride (5.5 g of 50% in oil, washed with ether to remove the oil) was added. The reaction was quenched with acetic acid (6.0 mL), the THF was removed under reduced pressure, and the residue was partitioned between ethyl acetate and water. The ethyl acetate was evaporated and the residual solid was crystallized from ethyl acetate; Skellysolve B to give 11.1 g of 1-(2-propynyl)-2-imidazolidinone, m.p. 110°-115° C. sodium hydride (5.5 g of 50% in oil, washed with ether to remove the oil) was added The reaction was quenched with acetic acid (6.0 mL) the THF was removed under reduced pressure the residue was partitioned between ethyl acetate and water The ethyl acetate was evaporated the residual solid was crystallized from ethyl acetate

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

Procedure: Chloroethyl isocyanate (12.2 g, 0.11 mol) was added at 0° C. to a stirred solution of propargylamine (6.6 g, 0.12 mol) in THF (200 mL). The solution was allowed to warm to room temperature and sodium hydride (5.5 g of 50% in oil, washed with ether to remove the oil) was added. The reaction was quenched with acetic acid (6.0 mL), the THF was removed under reduced pressure, and the residue was partitioned between ethyl acetate and water. The ethyl acetate was evaporated and the residual solid was crystallized from ethyl acetate; Skellysolve B to give 11.1 g of 1-(2-propynyl)-2-imidazolidinone, m.p. 110°-115° C. sodium hydride (5.5 g of 50% in oil, washed with ether to remove the oil) was added The reaction was quenched with acetic acid (6.0 mL) the THF was removed under reduced pressure the residue was partitioned between ethyl acetate and water The ethyl acetate was evaporated the residual solid was crystallized from ethyl acetate

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

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

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-(2-diethylaminoethyl)-4-trifluoromethyl-6-iodo-3-hydroxy-3-(2-chlorophenyl)oxindole (720 mg, 0.13 mmol), 3-(2-oxo-1-imidazolidinyl)-1-propyne (280 mg, 0.226 mmol), triethylamine (1 mL), CuI (12.8 mg, 0.0372 mmol), and (PPh3)2PdCl2 (22.6 mg, 0.0322 mmol) in a mixed solvent of THF (0.5 mL) and toluene (0.5 mL) was stirred for 3 h at 50° C. Water and sat. aqueous NaHCO3 were added and the mixture was extracted with ethyl acetate. The extracts were dried over MgSO4 and concentrated. The residue was purified by silica gel column chromatography with 30:1 to 20:1 chloroform/methanol to give the title compound (625 mg). The compound was dissolved in dioxane (4 mL) and 4 N HCl in dioxane (1.5 mL) was added. The solvent was evaporated azeotropically with toluene. The residual solid was washed with ether and dried in vacuo to give the hydrochloride (583 mg, 77%). the mixture was extracted with ethyl acetate The extracts were dried over MgSO4 concentrated The residue was purified by silica gel column chromatography with 30:1 to 20:1 chloroform/methanol

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

Procedure: To a suspension of ethylene urea (2.0 g, 23.2 mmol) in THF (80 mL) was added dropwise 1.47 N n-BuLi in hexane (15.8 mL, 23.2 mmol) at room temperature. 3-Bromopropyne (2.0 mL, 22.4 mmol) was added and the mixture was stirred for 30 min at room temperature then for 2 h at 50° C. Aqueous 5% KHSO4 was added and the mixture was extracted with ethyl acetate. The Organic layers were dried over MgSO4 and concentrated. The residue was purified by silica gel column chromatography with 1:1 to 0:1 hexane/ethyl acetate to give the title compound (641 mg, 22%). for 2 h at 50° C the mixture was extracted with ethyl acetate The Organic layers were dried over MgSO4 concentrated The residue was purified by silica gel column chromatography with 1:1 to 0:1 hexane/ethyl acetate