6,6-dimethyl-5,7-dioxaspiro[2.5]octane-4,8-dione

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 6,6-dimethyl-5,7-dioxaspiro[2,5]-octane-4,8-dione (1.02 g, 6.0 mmol, Aldrich) in 3 mL of DMF was added 4-fluorobenzenamine (666 mg, 6.0 mmol, Aldrich). The reaction mixture was stirred at rt overnight. The reaction mixture was poured into cold water (10 mL). The precipitate that formed was collected by filtration, washed with water, and dried under vacuum to afford the desired product (980 mg, 73%) as a tan solid. MS(ESI+) m/z 224.3 (M+H)+. The precipitate that formed was collected by filtration washed with water dried under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Following the procedure described in S. Danishefsky and R. K. Singh, J. American Chemical Society, 97:3239-3241(1975), a mixture of 0.5 g of 4-benzylpiperidine, 10 mL of toluene, and 0.5 g, of 6,6-dimethyl-5,7-dioxaspiro[2.5]octane 4,8-dione was stirred for 20 h, cooled, and, the white solid product collected by filtration and dried under vacuum. The yield of 5-[2-(4-benzyl-piperidin-1-yl)-ethyl]-2,2-dimethyl-[1,3]dioxane-4,6-dione was 0.94 g. cooled the white solid product collected by filtration dried under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Following the procedure described in S. Danishefsky and R. K. Singh, J. American Chemical Society, 97:3239-3241(1975), a mixture of 0.5 g of 4-benzylpiperidine, 10 mL of toluene, and 0.5 g, of 6,6-dimethyl-5,7-dioxaspiro[2.5]octane 4,8-dione was stirred for 20 h, cooled, and, the white solid product collected by filtration and dried under vacuum. The yield of 5-[2-(4-benzyl-piperidin-1-yl)-ethyl]-2,2-dimethyl-[1,3]dioxane-4,6-dione was 0.94 g. cooled the white solid product collected by filtration dried under vacuum

反応条件: temp:22.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 3-trifluoromethyl-phenylamine (2.8 g, 17.5 mmol) and 6,6-dimethyl-5,7-dioxa-spiro[2.5]octane-4,8-dione (1.0 g, 5.8 mmol) was stirred at 20-25° C. for 18 hrs. The reaction mixture was diluted with dichloromethane and washed with 10% NaOH solution (3×10 ml). The aqueous layer was cooled and acidified with dil HCl. The aqueous layer was extracted with dichloromethane, washed with saturated brine solution. The organic layer was dried over Na2SO4 and evaporated to obtain 2-oxo-1-(3-trifluoromethyl-phenyl)-pyrrolidine-3-carboxylic acid (1.1 g, 69%) as an off white solid. washed with 10% NaOH solution (3×10 ml) The aqueous layer was cooled The aqueous layer was extracted with dichloromethane washed with saturated brine solution The organic layer was dried over Na2SO4 evaporated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-amino-6,8-dichloropurine (2.04 g), 6,6-dimethyl-5,7-dioxaspiro[2.5]octane-4,8-dione (1.73 g) and anhydrous potassium carbonate (2.12 g) in N,N-dimethylformamide (40 ml) was stirred at room temperature for 18 hours under dry nitrogen. The solvent was evaporated and the residue dissolved in water (60 ml) and acidified from pH 10 to pH 4 with dilute hydrochloric acid. The yellow precipitate was filtered off, washed with water and dried to give 2-amino-6,8-dichloro-9-[1-(2,2-dimethyl-1,3-dioxane4,6-dione-5-yl)eth-2-yl]purine (2.2 g, 50%). T.1.c. r.f. 0.65 (25% methanol-dichloromethane). The solvent was evaporated the residue dissolved in water (60 ml) The yellow precipitate was filtered off washed with water dried

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 8-(4-amino-benzyl)-1-benzyl-3-butyl-3,7-dihydro-purine-2,6-dione (60 mg) in N,N-dimethylformamide (2 mL) was added 6,6-dimethyl-5,7-dioxa-spiro[2.5]octane-4,8-dione (Lancaster) (34 mg) and the mixture heated to 100° C. under argon for 16 hrs. The reaction mixture was cooled to RT and poured into saturated aqueous ammonium chloride, diluted with water and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (sodium sulfate) and concentrated in vacuo. Purification by chromatotron using a 2 mm silica plate eluted with 95:5 chloroform/methanol gave the desired product as a pale yellow solid (36 mg). MS, m/z(M+)=471.2272. The reaction mixture was cooled to RT extracted with ethyl acetate The combined organic extracts were washed with brine dried (sodium sulfate) concentrated in vacuo Purification by chromatotron eluted with 95:5 chloroform/methanol

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 8-(4-amino-benzyl)-1-benzyl-3-butyl-3,7-dihydro-purine-2,6-dione (60 mg) in N,N-dimethylformamide (2 mL) was added 6,6-dimethyl-5,7-dioxa-spiro[2.5]octane-4,8-dione (Lancaster) (34 mg) and the mixture heated to 100° C. under argon for 16 hrs. The reaction mixture was cooled to RT and poured into saturated aqueous ammonium chloride, diluted with water and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (sodium sulfate) and concentrated in vacuo. Purification by chromatotron using a 2 mm silica plate eluted with 95:5 chloroform/methanol gave the desired product as a pale yellow solid (36 mg). MS, m/z(M+)=471.2272. The reaction mixture was cooled to RT extracted with ethyl acetate The combined organic extracts were washed with brine dried (sodium sulfate) concentrated in vacuo Purification by chromatotron eluted with 95:5 chloroform/methanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 6,6-dimethyl-5,7-dioxaspiro[2,5]-octane-4,8-dione (1.02 g, 6.0 mmol, Aldrich) in 3 mL of DMF was added 4-fluorobenzenamine (666 mg, 6.0 mmol, Aldrich). The reaction mixture was stirred at rt overnight. The reaction mixture was poured into cold water (10 mL). The precipitate that formed was collected by filtration, washed with water, and dried under vacuum to afford the desired product (980 mg, 73%) as a tan solid. MS(ESI+) m/z 224.3 (M+H)+. The precipitate that formed was collected by filtration washed with water dried under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: This compound was prepared according to general method 1 starting from 6,6-dimethyl-5,7-dioxaspiro[2.5]octane-4,8-dione (0.250 g; 1.45 mmol) and 3,4-dimethylaniline (0.540 g; 4.36 mmol) in ethanol (3 mL). 1-(3,4-dimethylphenyl)-2-oxopyrrolidine-3-carboxylic acid 0.292 g (86%) was obtained as a white solid. This compound was prepared

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: This compound was prepared according to general method 1 starting from 6,6-dimethyl-5,7-dioxaspiro[2.5]octane-4,8-dione (0.250 g; 1.45 mmol) and 3,5-difluoroaniline (0.575 g; 4.36 mmol) in ethanol (3 mL). 1-(3,5-difluorophenyl)-2-oxopyrrolidine-3-carboxylic acid 0.167 g (48%) was obtained as a white solid. This compound was prepared

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: This compound was prepared according to general method 1 starting from 6,6-dimethyl-5,7-dioxaspiro[2.5]octane-4,8-dione (0.250 g; 1.45 mmol) and 2,3-dihydro-1H-inden-5-amine (0.593 g; 4.36 mmol) in ethanol (3 mL). 1-(2,3-dihydro-1H-inden-5-yl)-2-oxopyrrolidine-3-carboxylic acid 0.255 g (71%) was obtained as a white solid. This compound was prepared