N',N',2,2-tetramethylpropane-1,3-diamine

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:

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A resealable pressure vial was charged with N-(4-(3-(2-(methylsulfonyl)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-phenylphthalazin-1-amine (100 mg, 0.180 mmol) and N1,N1,2,2-tetramethylpropane-1,3-diamine (0.12 ml, 0.73 mmol) and DMSO (1.2 ml, 0.15 M). The reaction vessel was sealed and the mixture was stirred at 70° C. for 16 hrs. The reaction was cooled to RT and diluted with 3 ml of DMSO. The solution was purified by Gilson reverse phase chromatography (10% to 90% CH3CN/H2O/0.1% TFA). The product-containing fractions were combined, basified by addition of aq. NaHCO3 and extracted with ethyl acetate. The organic portion was dried with Na2SO4, filtered, and concentrated to afford pure N-(4-(3-(2-(3-(dimethylamino)-2,2-dimethylpropylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-phenylphthalazin-1-amine as a yellow solid. MS m/z=597 [M+H]+. Calc'd for C36H36N80: 596.72. The reaction vessel was sealed The reaction was cooled to RT The solution was purified by Gilson reverse phase chromatography (10% to 90% CH3CN/H2O/0.1% TFA) basified by addition of aq. NaHCO3 extracted with ethyl acetate The organic portion was dried with Na2SO4 filtered concentrated

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A resealable pressure vial was charged with N-(4-(3-(2-(methylsulfonyl)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-phenylphthalazin-1-amine (100 mg, 0.180 mmol) and N1,N1,2,2-tetramethylpropane-1,3-diamine (0.12 ml, 0.73 mmol) and DMSO (1.2 ml, 0.15 M). The reaction vessel was sealed and the mixture was stirred at 70° C. for 16 hrs. The reaction was cooled to RT and diluted with 3 ml of DMSO. The solution was purified by Gilson reverse phase chromatography (10% to 90% CH3CN/H2O/0.1% TFA). The product-containing fractions were combined, basified by addition of aq. NaHCO3 and extracted with ethyl acetate. The organic portion was dried with Na2SO4, filtered, and concentrated to afford pure N-(4-(3-(2-(3-(dimethylamino)-2,2-dimethylpropylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-phenylphthalazin-1-amine as a yellow solid. MS m/z=597 [M+H]+. Calc'd for C36H36N80: 596.72. The reaction vessel was sealed The reaction was cooled to RT The solution was purified by Gilson reverse phase chromatography (10% to 90% CH3CN/H2O/0.1% TFA) basified by addition of aq. NaHCO3 extracted with ethyl acetate The organic portion was dried with Na2SO4 filtered concentrated

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

Procedure: Using the compound obtained in Example 2-13 step (i) (350 mg), N,N,2,2-tetramethylpropane-1,3-diamine (1 ml), potassium carbonate (500 mg) and methyl[3-(bromomethyl)phenyl]acetate (200 mg), the same manner to Example 2-29 was conducted to give the titled compound as a white solid. Yield: 60 mg (13%); MS APCI+ve 570 (M+H).

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

Procedure: 426 g (3 mols) of butyl methacrylate, 390 g (3 mols) of N,N,2,2-tetramethylpropane-1,3-diamine, 29.4 g (0.3 mol) of H3PO4, and 2 g of hydroquinone were warmed for 2 hours at 220° C. N-(3-dimethylamino-2,2-dimethylpropyl)-methacrylic acid amide was formed in this way. Yield: 60% (selectivity: 94% calculated on the reacted butyl methacrylate).