4,4-dimethylpyrrolidin-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: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: The title compound, light brown oil, MS: m/e=305.2 (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 4,4-dimethyl-pyrrolidin-2-one.

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

Procedure: The title compound, light brown oil, MS: m/e=305.2 (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 4,4-dimethyl-pyrrolidin-2-one.

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

Procedure: To a suspension of 5-bromo-2-phenylethynyl-pyridine (Example 1, step 1) (40 mg, 0.155 mmol), 4,4-dimethylpyrrolidine-2-one (21 mg, 0.186 mmol, 1.2 equiv.), potassium carbonate (64 mg, 0.465 mmol, 3 equiv.) and N,N′-dimethylethylenediamine (1.4 mg, 0.015 mmol, 0.1 equiv.) in 1 ml of dioxane was added under argon atmosphere copper(I)iodide (3 mg, 0.015 mmol, 0.1 equiv.). The mixture was stirred overnight at 100° C. The reaction mixture was cooled and extracted with saturated NaHCO3 solution and two times with ethyl acetate. The organic layers were extracted with brine, combined, dried over sodium sulfate and evaporated to dryness. The crude product was purified by flash chromatography on a silica gel column eluting with a heptane:ethyl acetate gradient 100:0 to 30:70. The desired 4,4-dimethyl-1-(6-phenylethynyl-pyridin-3-yl)-pyrrolidin-2-one (30 mg, 67% yield) was obtained as a white solid, MS: m/e=291.1 (M+H30). The reaction mixture was cooled extracted with saturated NaHCO3 solution and two times with ethyl acetate The organic layers were extracted with brine dried over sodium sulfate evaporated to dryness The crude product was purified by flash chromatography on a silica gel column eluting with a heptane

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-chloro-6-(phenylethynyl)pyridazine (CAS 77778-15-5) (180 mg, 839 μmol) and 4,4-dimethylpyrrolidin-2-one (CAS 66899-02-3) (142 mg, 1.26 mmol, 1.5 equiv.) in 2 ml of DMF were added cesium carbonate (546 mg, 1.68 mmol, 2 equiv.). The suspension was heated 16 hours at 120° C. and then allowed to cool to room temperature. Ethyl acetate (10 ml) were added and the unsoluble salts were filtered off. After concentration in vaccuo, the residue was dissolved in 10 ml of ethyl acetate. Silicagel (4 g) were added and the suspension was evaporated to dryness. The silicagel with the adsorbed crude mixture was loaded onto a 20 g silicagel flash chromatography column and eluted three min. with heptane followed by a heptane to 45% ethyl acetate/heptane gradient over 25 min to yield 36 mg (15% yield) of the title compound as a cristalline yellow solid, MS: m/e=292.3 (M+H+). to cool to room temperature the unsoluble salts were filtered off After concentration in vaccuo the residue was dissolved in 10 ml of ethyl acetate Silicagel (4 g) were added the suspension was evaporated to dryness eluted three min. with heptane

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (200 mg, 0.78 mmol) 2-Bromo-5-trimethylsilanylethynyl-pyrimidine (Example 120, step 1) was dissolved in toluene (7 ml) and 4,4-dimethylpyrrolidin-2-one (89 mg, 0.78 mmol, 1.0 equiv.), cesium carbonate (410 mg, 1.25 mmol, 1.6 equiv.), xantphos (CAS 161265-03-8) (18 mg, 0.03 mmol, 0.04 equiv.) and Pd2(dba)3 (14 mg, 0.01 mmol, 0.02 equiv.) were added under nitrogen. The mixture was stirred for 2 hours at 90° C. The crude product was purified by flash chromatography by directly loading the toluene mixture onto a silica gel column and eluting with an ethyl acetate:heptane gradient 0:100 to 100:0. The desired 4,4-dimethyl-1-(5-trimethylsilanylethynyl-pyrimidin-2-yl)-pyrrolidin-2-one (164 mg, 73% yield) was obtained as a light red solid, MS: m/e=288.1 (M+H+). The crude product was purified by flash chromatography eluting with an ethyl acetate