3-amino-N,N-dimethylbenzamide

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: To a stirred solution of 3-amino-N,N-dimethylbenzamide (1.3 g) in 1,4-dioxane(20 ml) was added 1N sodium hydroxide (23.4 ml) and phenyl chloroformate (1.5 ml) successively in an ice-cooled bath. The bath was removed and the reaction mixture was stirred vigorously for 3 hours during which time, phenyl chloroformate (0.7 ml) was further added. The mixture was extracted with ethyl acetate and the organic layer was washed with water and saturated sodium chloride solution. After dried over anhydrous magnesium sulfate and filtered, the solvent was removed in vacuo and the residual oil was purified by flash chromatography eluting with ethyl acetate-n-hexane (2:1, V/V) to give a solid, which was recrystallized from benzene-n-hexane (5:1, V/V) to afford phenyl 3-(dimethylcarbamoyl)phenylcarbamate (1.4 g) as a colorless powder. cooled bath The bath was removed was further added The mixture was extracted with ethyl acetate the organic layer was washed with water and saturated sodium chloride solution After dried over anhydrous magnesium sulfate filtered the solvent was removed in vacuo the residual oil was purified by flash chromatography eluting with ethyl acetate-n-hexane (2:1, V/V) to give a solid, which was recrystallized from benzene-n-hexane (5:1, V/V)

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

Procedure: To a stirred solution of 3-amino-N,N-dimethylbenzamide (1.3 g) in 1,4-dioxane(20 ml) was added 1N sodium hydroxide (23.4 ml) and phenyl chloroformate (1.5 ml) successively in an ice-cooled bath. The bath was removed and the reaction mixture was stirred vigorously for 3 hours during which time, phenyl chloroformate (0.7 ml) was further added. The mixture was extracted with ethyl acetate and the organic layer was washed with water and saturated sodium chloride solution. After dried over anhydrous magnesium sulfate and filtered, the solvent was removed in vacuo and the residual oil was purified by flash chromatography eluting with ethyl acetate-n-hexane (2:1, V/V) to give a solid, which was recrystallized from benzene-n-hexane (5:1, V/V) to afford phenyl 3-(dimethylcarbamoyl)phenylcarbamate (1.4 g) as a colorless powder. cooled bath The bath was removed was further added The mixture was extracted with ethyl acetate the organic layer was washed with water and saturated sodium chloride solution After dried over anhydrous magnesium sulfate filtered the solvent was removed in vacuo the residual oil was purified by flash chromatography eluting with ethyl acetate-n-hexane (2:1, V/V) to give a solid, which was recrystallized from benzene-n-hexane (5:1, V/V)

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

Procedure: To a stirred solution of 3-amino-N,N-dimethylbenzamide (1.3 g) in 1,4-dioxane(20 ml) was added 1N sodium hydroxide (23.4 ml) and phenyl chloroformate (1.5 ml) successively in an ice-cooled bath. The bath was removed and the reaction mixture was stirred vigorously for 3 hours during which time, phenyl chloroformate (0.7 ml) was further added. The mixture was extracted with ethyl acetate and the organic layer was washed with water and saturated sodium chloride solution. After dried over anhydrous magnesium sulfate and filtered, the solvent was removed in vacuo and the residual oil was purified by flash chromatography eluting with ethyl acetate--n-hexane (2:1, V/V) to give a solid, which was recrystallized from benzene--n-hexane (5:1, V/V) to afford phenyl 3-(dimethylcarbamoyl)phenylcarbamate (1.4 g) as a colorless powder. mp: 151.2-153.0° C. cooled bath The bath was removed was further added The mixture was extracted with ethyl acetate the organic layer was washed with water and saturated sodium chloride solution After dried over anhydrous magnesium sulfate filtered the solvent was removed in vacuo the residual oil was purified by flash chromatography eluting with ethyl acetate--n-hexane (2:1, V/V) to give a solid, which was recrystallized from benzene--n-hexane (5:1, V/V)

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

Procedure: To a stirred solution of 3-amino-N,N-dimethylbenzamide (1.3 g) in 1,4-dioxane(20 ml) was added 1N sodium hydroxide (23.4 ml) and phenyl chloroformate (1.5 ml) successively in an ice-cooled bath. The bath was removed and the reaction mixture was stirred vigorously for 3 hours during which time, phenyl chloroformate (0.7 ml) was further added. The mixture was extracted with ethyl acetate and the organic layer was washed with water and saturated sodium chloride solution. After dried over anhydrous magnesium sulfate and filtered, the solvent was removed in vacuo and the residual oil was purified by flash chromatography eluting with ethyl acetate--n-hexane (2:1, V/V) to give a solid, which was recrystallized from benzene--n-hexane (5:1, V/V) to afford phenyl 3-(dimethylcarbamoyl)phenylcarbamate (1.4 g) as a colorless powder. mp: 151.2-153.0° C. cooled bath The bath was removed was further added The mixture was extracted with ethyl acetate the organic layer was washed with water and saturated sodium chloride solution After dried over anhydrous magnesium sulfate filtered the solvent was removed in vacuo the residual oil was purified by flash chromatography eluting with ethyl acetate--n-hexane (2:1, V/V) to give a solid, which was recrystallized from benzene--n-hexane (5:1, V/V)

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

Procedure: To a stirred solution of 3-amino-N,N-dimethylbenzamide (1.3 g) in 1,4-dioxane(20 ml) was added 1N sodium hydroxide (23.4 ml) and phenyl chloroformate (1.5 ml) successively in an ice-cooled bath. The bath was removed and the reaction mixture was stirred vigorously for 3 hours during which time, phenyl chloroformate (0.7 ml) was further added. The mixture was extracted with ethyl acetate and the organic layer was washed with water and saturated sodium chloride solution. After dried over anhydrous magnesium sulfate and filtered, the solvent was removed in vacuo and the residual oil was purified by flash chromatography eluting with ethyl acetate-n-hexane (2:1, V/V) to give a solid, which was recrystallized from benzene-n-hexane (5:1, V/V) to afford phenyl 3-(dimethylcarbamoyl)phenylcarbamate (1.4 g) as a colorless powder. cooled bath The bath was removed was further added The mixture was extracted with ethyl acetate the organic layer was washed with water and saturated sodium chloride solution After dried over anhydrous magnesium sulfate filtered the solvent was removed in vacuo the residual oil was purified by flash chromatography eluting with ethyl acetate-n-hexane (2:1, V/V) to give a solid, which was recrystallized from benzene-n-hexane (5:1, V/V)

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

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

Procedure: 8-Indan-5-yl-2-methanesulfonyl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester (20 mg, 0.048 mmol) and 3-amino-N,N-dimethyl-benzamide (8 mg, 0.05 mmol) were combined in i-PrOH (2 mL) and heated to 90° C. After 15 h, the reaction mixture was concentrated and purified by preparative HPLC (C-18 column, 32 mL/min 5-100% MeCN/H2O gradient over 15 min) and lyophilized to provide 15.6 mg of 2-(3-dimethylcarbamoyl-phenylamino)-8-indan-5-yl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester. 1H NMR (400 MHz, CDCl3) δ (ppm): 9.31 (s, 1H), 1.13 (s, 1H), 7.46 (br s, 1H), 7.33 (d, 1H, J=7.9 Hz), 7.16-7.21 (m, 2H), 7.10 (d, 1H, J=7.6 Hz), 6.96 (br s, 2H), 4.29 (q, 2H, J=7.1 Hz), 2.97-3.04 (m, 5H), 2.85-2.93 (m, 5H), 2.14 (p, 2H, J=7.4 Hz), 1.29 (t, 3H, J=7.1 Hz) the reaction mixture was concentrated purified by preparative HPLC (C-18 column, 32 mL/min 5-100% MeCN/H2O gradient over 15 min)

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

Procedure: A stirred suspension of lithium aluminium hydride (0.24 g, 6.3 mmol) in tetrahydrofuran (THF) (15 ml) at 0° C. under Argon, was treated dropwise over a period of fifteen minutes, with a solution of N,N-Dimethyl-3-aminobenzamide (D24) (0.68 g, 4.2 mmol) in THF (15 ml). The reaction mixture was allowed to warm to room temperature after which it was heated to reflux for 2 hours. The reaction mixture was allowed to cool to room temperature then treated sequentially with water (0.24 ml), 10% sodium hydroxide solution (0.24 ml) then water (0.72 ml). The reaction mixture was filtered through kieselguhr and the filtrate dried (Na2SO4) and concentrated in vacuo to afford the title compound as a pale brown oil (0.55 g, 87%). was heated to reflux for 2 hours to cool to room temperature The reaction mixture was filtered through kieselguhr the filtrate dried (Na2SO4) concentrated in vacuo

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

Procedure: N,N-Dimethyl-3-nitrobenzamide (D23) (0.94 g, 4.8 mmol) was hydrogenated in ethanol (100 ml) over 10% Palladium-Charcoal (0.25 g) for 1 hour. The catalyst was removed by filtration through Kieselguhr, and the filtrate concentrated in vacuo to afford the title compound as a light brown solid (0.68 g, 87%). The catalyst was removed by filtration through Kieselguhr the filtrate concentrated in vacuo