2H-2,3-dinitrogen phenodiazine-1-ketone and using method thereof
A kind of technology of heteroaryl and R12, applied in the field of 2H-2
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Embodiment 1
[0537] This example illustrates the preparation of 4-diamine substituted 2H-2,3-phthalazin-1-ones.
[0538]
[0539] 4-(3-Amino-propylhydrogen)-2H-2,3-naphthyridine-1-one (R=H)
[0540] A 2-liter three-necked round-bottom flask was equipped with a mechanical stirrer and a thermometer, and 1,3-propanediamine (66.0 g, 0.890 mol) and ethanol (450 ml) were put into the flask. Phthalic anhydride (120 g, 0.811 mol) was then added in portions over 20 minutes. An exothermic reaction occurred, forming a viscous white precipitate. Stirring was continued for an additional hour and the resulting precipitate was vacuum filtered. The filter cake was washed with ethanol (2 x 100ml) to provide 178g of a white solid which was used directly. The above solid (50.0 g) and ethylene glycol (200 ml) were put into a 1-liter three-necked round-bottom flask equipped with a mechanical stirrer and a thermostat, and the reaction mixture was refluxed at 170° C. for 1 hour. The volatiles were distill...
Embodiment 2
[0546] This example illustrates the preparation of diamine-substituted 2H-2,3-phthalazin-1-ones using cyanobenzoate compounds.
[0547]
[0548] Methods for I and III:
[0549] A mixture of methyl 2-cyano-benzoate (2g, 12.4mmol) and butane-1,4-diamine (1.09g, 12.4mmol) was heated in DMF (10ml) at 80°C overnight. Dichloromethane (i.e. DCM) was added, and the organic layer was washed with saturated NaHCO 3 , 10% citric acid and brine washes in MgSO 4 Dry, filter and concentrate. Purified by silica gel column chromatography (CH 2 Cl 2 to CH 2 Cl 2 / MeOH gradient, 98 / 2), afforded 600 mg of cyclized material (24% yield). Treatment of this material with hydrazine hydrate as described in Example 1 affords 4-(4-amino-butylamino)-2H-2,3-naphthyridine-1-one. Method for IV and VII (1,3-cyclohexanediamine and 1,3-diamino-2-propanol):
[0550] To a solution of methyl 2-cyanobenzoate (322 mg, 2.00 mmol) in DMF (1 ml) was added 1,3-cyclohexanediamine (285 mg, 2.50 mmol). The rea...
Embodiment 3
[0554] Method for IX, X, XI
[0555] This example illustrates the preparation of diamine-substituted 2H-2,3-phthalazin-1-ones using mono-protected diamine compounds
[0556]
[0557]
[0558] Combine 2-cyano-benzoic acid methyl ester (0.40 g, 2.48 mmol) and 2.48 mmol amine ((3-aminomethyl-phenyl)-carbamic acid tert-butyl ester or (3-amino -propyl)-methyl-carbamic acid tert-butyl ester or 4-aminomethyl-piperidine-1-carboxylic acid tert-butyl ester). Add 2.73mmol NaOMe (as a 0.5M solution) and stir at room temperature for 3-18 hours. The solvent was removed in vacuo and washed with EtOAc (100ml) and 0.5M NaHSO 4 (2 x 15ml) followed by brine (1 x 15ml) extraction. The organic layer was dried (MgSO 4 ) and concentrated in vacuo.
[0559]
[0560] The crude 3-alkylimino-2,3-dihydro-isoindol-1-one (1.22 mmol) and hydrazine hydrate (3.65 mmol) produced above were combined in 5 ml of MeOH and heated to 85 °C for 18 Hour. Filter the product with H 2 O washing.
[0561...
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