[CH3:1][CH:2]([CH3:16])[CH2:3][CH2:4][N:5]1[C:13](=[O:14])O[C:11](=[O:15])[C:10]2[N:6]1[CH:7]=[CH:8][CH:9]=2.C(OCC)(=O)[CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20].[H-].[Na+]>CN(C)C(=O)C.CO>[CH2:22]([O:21][C:19]([C:18]1[C:13](=[O:14])[N:5]([CH2:4][CH2:3][CH:2]([CH3:1])[CH3:16])[N:6]2[CH:7]=[CH:8][CH:9]=[C:10]2[C:11]=1[OH:15])=[O:20])[CH3:23]
To a solution of 4-(3-methyl-butyl)-6-oxa-3a,4-diaza-indene-5,7-dione (Example 1e, 0.080 g, 0.36 mmol) and diethyl malonate (0.58 mL, 3.6 mmol) in N,N-dimethylacetamide (1 mL) was added sodium hydride (0.017 g, 0.43 mmol) and 1 drop of methanol. The reaction mixture was heated to 120° C. and stirred for 16 h. The reaction was allowed to cool to 25° C. and quenched with saturated aqueous ammonium chloride solution and ethyl acetate. The layers were separated and the aqueous layer was extracted with ethyl acetate (3×3 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (Merck silica gel 60, 40-63 μm, ethyl acetate/dichloromethane, 2-5%) to afford the desired product, 4-hydroxy-1-(3-methyl-butyl)-2-oxo-1,2-dihydro-pyrrolo[1,2-b]pyridazine-3-carboxylic acid ethyl ester (0.058 g, 0.20 mmol, 55% yield) as a light tan solid. 1H NMR (400 MHz, DMSO-d6) δ 0.93 (6H, d, J=6.4 Hz), 1.30 (3H, t, J=6.8 Hz), 1.49 (2H, q, J1=15.2 Hz, J2=7.6 Hz), 1.63 (1H, m), 4.23-4.30 (4H, m), 6.56 (1H, m), 6.87 (1H, m), 7.68 (1H, m); LC-MS (ESI) calcd for C15H20N2O4 292.33. found 293.30 [M+H+].
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