1-methylimidazolidin-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:

Conditions: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 2 mL glass microwave reaction vessel are placed in (2R,4S)-4-[(3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amino]-2-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (200 mg, 0.32 mmol), 1-Methyl-imidazolidin-2-one (35 mg, 0.35 mmol), CuI (123.4 mg, 0.35 mmol), trans-1,2-cyclohexane (0.005 mL, 0.35 mmol), K2CO3 (88 mg, 0.64 mmol) in dry dioxane (2 mL). The reaction vessel is sealed and heated under microwave irradiation at 180° C. for 20 min. After completion of the reaction, the solvent is diluted with EtOAc and washed with sat. NH3 (aq.), water, dried (Na2SO4), and concentrated under reduced pressure. The residue is purified by flash chromatography on silica gel to give (2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(3-methyl-2-oxo-imidazolidin-1-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (120 mg, 61%). The reaction vessel is sealed After completion of the reaction washed with sat. NH3 (aq.), water dried (Na2SO4) concentrated under reduced pressure The residue is purified by flash chromatography on silica gel

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

Procedure: The title compound, light brown solid, MS: m/e=293.1 (M+H+), can be prepared in accordance with the general method of example 31, step 2 from (5-phenylethynyl-pyridin-2-yl)-methanol (example 31, step 1) and 1-methyl-imidazolidin-2-one.

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

Procedure: The title compound, light brown solid, MS: m/e=293.1 (M+H+), can be prepared in accordance with the general method of example 31, step 2 from (5-phenylethynyl-pyridin-2-yl)-methanol (example 31, step 1) and 1-methyl-imidazolidin-2-one.

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

Procedure: Prepared according to the procedure described in Example 116, Step 1, using the following starting materials: [3-(4-bromo-2-bromomethyl-phenoxy)-4-methoxy-phenyl]-acetic acid ethyl ester and 1-methyl-2-imidazolidinone. Prepared

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

Procedure: This product, a liquid, was prepared according to Example 1 by substituting dimethylamine for pyrrolidine and 1-t-butyoxycarbonyl-2-imidazolidinone for 1-methyl-2-imidazolidinone. This product, a liquid, was prepared

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

Procedure: A suspension of potassium hydride (10.44 g of a 35% by wt suspension in mineral oil, washed with ether to remove oil, 0.09 mol) in dry THF (50 mL) was added dropwise, with cooling, to a stirred solution of 1-methyl-2-imidazolidinone (7.6 g, 0.076 mol) in dry THF (150 mL). After warming to room temperature and stirring for 20 min, the reaction was cooled again and propargyl bromide (13.54 g of an 80% solution in toluene, 0.09 mol) was added dropwise. The reaction was then allowed to slowly warm to room temperature and was stirred for 0.5 hr. The reaction was quenched with methanol and water and the solvents were removed under reduced pressure. The residual oil was partitioned between ethyl acetate and water; evaporation of the organic phase gave 10.65 g crude product. The compound was purified by chromatography on silica gel in chloroform to get 4.51 g of crystalline product. washed with ether to remove oil, 0.09 mol) in dry THF (50 mL) was added dropwise the reaction was cooled again to slowly warm to room temperature was stirred for 0.5 hr The reaction was quenched with methanol and water the solvents were removed under reduced pressure The residual oil was partitioned between ethyl acetate and water evaporation of the organic phase gave 10.65 g crude product The compound was purified by chromatography on silica gel in chloroform

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

Procedure: A suspension of potassium hydride (10.44 g of a 35% by wt suspension in mineral oil, washed with ether to remove oil, 0.09 mol) in dry THF (50 mL) was added dropwise, with cooling, to a stirred solution of 1-methyl-2-imidazolidinone (7.6 g, 0.076 mol) in dry THF (150 mL). After warming to room temperature and stirring for 20 min, the reaction was cooled again and propargyl bromide (13.54 g of an 80% solution in toluene, 0.09 mol) was added dropwise. The reaction was then allowed to slowly warm to room temperature and was stirred for 0.5 hr. The reaction was quenched with methanol and water and the solvents were removed under reduced pressure. The residual oil was partitioned between ethyl acetate and water; evaporation of the organic phase gave 10.65 g crude product. The compound was purified by chromatography on silica gel in chloroform to get 4.51 g of crystalline product. washed with ether to remove oil, 0.09 mol) in dry THF (50 mL) was added dropwise the reaction was cooled again to slowly warm to room temperature was stirred for 0.5 hr The reaction was quenched with methanol and water the solvents were removed under reduced pressure The residual oil was partitioned between ethyl acetate and water evaporation of the organic phase gave 10.65 g crude product The compound was purified by chromatography on silica gel in chloroform

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

Procedure: A solution of 1-methylimidazolidin-2-one (80 mg, 0.82 mM, Heterocycles, 1987, 26, 3153) in dimethylsulfoxide (1 ml) was treated with sodium hydride (55% in oil, 40 mg, 0.92 mM) at ambient temperature under nitrogen. After stirring for 20 minutes, (5R)-3-(4-(3,6-dihydro-2H-pyran-4-yl)-3-fluorophenyl)-5-methanesulfonyloxymethyloxazolidin-2-one (300 mg, 0.81 mM; WO 97-09328) in dimethylsulfoxide (1.5 ml) was added and stirring continued for 1.5 hours. The temperature was then progressively raised to 85°, and heated at this temperature for 24 hours. After cooling and dilution with water (50 ml), the mixture was extracted with ethyl acetate (3×30 ml), and combined extracts washed with brine (20 ml). After drying (magnesium sulfate) and evaporation, the residue was purified by chromatography on a 10 g silica Mega Bond Elut® column, eluting with a gradient increasing in polarity from 0 to 6% methanol in dichloromethane. Relevant fractions were combined to give the title product (60 mg). stirring continued for 1.5 hours The temperature was then progressively raised to 85° heated at this temperature for 24 hours After cooling dilution with water (50 ml), the mixture was extracted with ethyl acetate (3×30 ml) washed with brine (20 ml) After drying (magnesium sulfate) and evaporation the residue was purified by chromatography on a 10 g silica Mega Bond Elut® column eluting with a gradient increasing in polarity from 0 to 6% methanol in dichloromethane