反应详情

3-Methyl-N-(1-phenylethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-amine (100 mg, 0.395 mmol), paraformaldehyde (119 mg, 3.95 mmol), NaBH4 (74.7 mg, 1.974 mmol) and anhydrous THF (5 mL) were charged into a disposable reaction tube equipped with a stirbar and a septum. TFA (2.5 mL) was slowly added at room temperature over 1 h and the reaction was stirred for an additional 18 h at room temperature. A 1M aqueous solution of NaOH was added until pH˜12 and the product was extracted with CH2Cl2/MeOH (19:1) (4×25 mL). The organic layers were combined, dried over Na2SO4 and concentrated to dryness. The crude product was then diluted with MeOH/H2O (19:1), filtered, purified by preparative HPLC (reverse phase) and lyophilized to give the N,3-dimethyl-N-(1-phenylethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-amine (Compound 2) as a white solid (6 mg; 6% yield). 1H NMR (400 MHz, DMSO-d6): δ 7.98 (d, J=10.1 Hz, 1H), 7.22-7.39 (m, 6H), 5.68 (q, J=6.9 Hz, 1H), 2.81 (s, 3H), 2.52 (s, 3H), 1.56 (d, J=7.1 Hz, 3H). LRMS [M+H]+: 268 m/z.

1. customequipped with a stirbar
2. extractionthe product was extracted with CH2Cl2/MeOH (19:1) (4×25 mL)
3. dry with materialdried over Na2SO4
4. concentrationconcentrated to dryness
5. additionThe crude product was then diluted with MeOH/H2O (19:1)
6. filtrationfiltered
7. custompurified by preparative HPLC (reverse phase)