反应详情

NaBH3CN (211 mg, 3.36 mmol) was added to a solution of (6-amino-3-aza-bicyclo[3.1.0]hex-3-yl)-(7-chloro-thieno[3,2-b]pyridin-2-yl)-methanone (250 mg, 0.85 mmol) and formaldehyde (1.14 mL, 17 mmol) in CH3CN at 0° C. After 30 min AcOH (0.5 mL) was added and the reaction mixture was allowed to warm to room temperature. After 1 h the reaction mixture was concentrated, and the resulting residue was dissolved in H20. The resulting aqueous layer was adjusted to pH 9 with 6N NaOH. The resulting solution was extracted with CH2Cl2 (2×) and the combined organic extracts were dried over Na2SO4, filtered, then concentrated. The resulting material was purified on silica gel by flash column chromatography CH2Cl2/MeOH (85/15) to afford the title compound as a white solid (44 mg, 16%). MS: 322.2/324.2 (MH+); HPLC Rf: 3.62 min.; HPLC purity 95%.

1. concentrationAfter 1 h the reaction mixture was concentrated
2. dissolutionthe resulting residue was dissolved in H20
3. extractionThe resulting solution was extracted with CH2Cl2 (2×)
4. dry with materialthe combined organic extracts were dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe resulting material was purified on silica gel by flash column chromatography CH2Cl2/MeOH (85/15)