2,4-dihydro-1H-isoquinolin-3-one

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A N,N-dimethylformamide (1 mL) solution containing 1,4-dihydro-3(2H)-isoquinolinone (300 mg, 2.04 mmol) and N,N-dimethylformamide dimethylacetal (0.65 mL, 4.89 mmol) is heated at 100° C. for 2.5 hours. After removing the solvents, the residue is washed with ether, water and ether to give 88 mg of the product as a pink solid. The filtrate is evaporated to dryness, and the residue is treated with ether, water and ether to give 105 mg of a second crop of the product with a total yield of 47% (193 mg); MS (ESI) m/z 203.2 (M+1). Ref: Chemistry of Heterocyclic compd. 370-374 (1981). After removing the solvents the residue is washed with ether, water and ether

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

実験手順: A N,N-dimethylformamide (1 mL) solution containing 1,4-dihydro-3(2H)-isoquinolinone (300 mg, 2.04 mmol) and N,N-dimethylformamide dimethylacetal (0.65 mL, 4.89 mmol) is heated at 100° C. for 2.5 hours. After removing the solvents, the residue is washed with ether, water and ether to give 88 mg of the product as a pink solid. The filtrate is evaporated to dryness, and the residue is treated with ether, water and ether to give 105 mg of a second crop of the product with a total yield of 47% (193 mg); MS (ESI) m/z 203.2 (M+1). Ref: Chemistry of Heterocyclic compd. 370-374 (1981). After removing the solvents the residue is washed with ether, water and ether

反応条件: temp:155.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of phenylacetamide (5 g, 37 mmol), pyrophosphonic acid (80 g, 449.5 mmol) and paraformaldehyde (1.22 g, 40.7 mmol) is heated at 155° C. for 1 h to give a viscous black solution. It is poured into ice water and treated with potassium carbonate to pH 7. The solution is extracted with ethyl acetate, and the organic solution is washed with saturated potassium carbonate, dried over magnesium sulfate, and evaporated to dryness to give 1.145 g (21%) of the product as a yellow solid; MS (ESI) m/z 148.0 (M+1). [Ref: Heterocycles 26(9), 2385 (1987)]. to give a viscous black solution The solution is extracted with ethyl acetate the organic solution is washed with saturated potassium carbonate dried over magnesium sulfate evaporated to dryness

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

実験手順: To a solution of 4-chloro-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine (20 mg, 0.09 mmol, Example 1) and 1,4-dihydroisoquinolin-3(2H)-one (16 mg, 0.10 mmol, Tyger, Cat. No. D30080) in 1,4-dioxane (1 mL) was added (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (20 mg, 0.04 mmol, Aldrich, Cat. No. 526460), palladium acetate (4 mg, 0.02 mmol, Aldrich, Cat. No. 205869) and cesium carbonate (60 mg, 0.2 mmol, Aldrich, Cat. No. 202126). The mixture was degassed with nitrogen and heated at 100° C. 20 h. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in MeOH, and purified by RP-HPLC (pH=10 system) to afford the desired compound. The mixture was degassed with nitrogen 20 h The reaction mixture was concentrated under reduced pressure The residue was dissolved in MeOH purified by RP-HPLC (pH=10 system)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of POCl3 (0.73 mL, 7.85 mmol, 3.8 eqiv.) and DMF (0.6 g, 8.16 mmol, 4.0 equiv.) in THF was added 1,2-dihydroisoquinolin-3-(4H)-one at 0° C. in portions for 5 min. The mixture was continued to stir at 0° C. for 1 h and poured into a mixture of 2 N NaOH (20 mL), ice (20 g), and toluene (20 mL). The organic phase was separated and the aqueous layer was extracted with toluene one more time. The combined organic layer was washed with water, dried over Na2SO4, and concentrated to half of its volume at low temperature in vacuo. To this mixture was added 2 N H2SO4 (20 mL) under vigorous stirring followed by ground KMnO4 in portions. The mixture was continued to stir for another 4 h. The organic phase was separated, dried over Na2SO4, and concentrated to give 3-chloroisoquinoline-4-carbaldehyde (220 mg, 50% pure) as a oil, which was used for next step without further purification. LRMS (M+H+) m/z 192.0. The organic phase was separated the aqueous layer was extracted with toluene one more time The combined organic layer was washed with water dried over Na2SO4 concentrated to half of its volume at low temperature in vacuo To this mixture was added 2 N H2SO4 (20 mL) under vigorous stirring to stir for another 4 h The organic phase was separated dried over Na2SO4 concentrated