反応 #58500

反応方程式

sodium triacetoxyborohydride

2,4,6-trifluoro-N-[6-(piperidin-4-ylcarbonyl)pyridin-2-yl]benzamide

cyclopropylmethanal

dichloromethane

acetic acid

→

title compound

収率 77.0%

2,4,6-Trifluoro-N-[6-(1-cyclopropylmethyl-piperidin-4-ylcarbonyl)-pyridin-2-yl]-benzamide dihydrochloride salt

収率 77.0%

溶媒

methanol

反応条件

後処理

1. 1
   workup.WAITAfter 3 hrs
2. 2
   洗浄Wash the column with methanol
3. 3
   洗浄elute with 2M ammonia/methanol
4. 4
   濃縮concentrate the eluent
5. 5
   その他Purify the residue by flash chromatography
6. 6
   洗浄eluting with 10% ammonia/methanol in dichloromethane

実験手順

Combine 2,4,6-trifluoro-N-[6-(piperidin-4-ylcarbonyl)pyridin-2-yl]benzamide (0.05 g, 0.138 mmol), cyclopropylmethanal (0.10 g, 1.38 mmol) and dichloromethane (5 mL), and stir at ambient temperature. After 15 minutes, add glacial acetic acid (0.02 mL, 0.35 mmol) followed by sodium-triacetoxyborohydride (0.038 g, 0.18 mmol) with stirring. After 3 hrs., dilute the reaction mixture with methanol (5 mL) and load on an SCX column (10 g). Wash the column with methanol, elute with 2M ammonia/methanol, and concentrate the eluent. Purify the residue by flash chromatography, eluting with 10% ammonia/methanol in dichloromethane, to obtain the free base of the title compound (0.045 g, 77%). Dissolve the free base in dichloromethane (5 mL), treat with 1M hydrogen chloride in diethylether (0.25 mL), and concentrate the mixture to obtain the dihydrochloride salt. M.p.=140° C.; HRMS: Obs. m/z 418.1743; Calc. m/z 418.1742; 1H NMR (CDCl3): 11.51 (bs, 1H), 10.34 (bs, 1H), 8.38 (m, 1H), 8.11 (m, 1H), 7.78(d, 1H), 7.42 (m, 2H), 3.79 (m, 1H), 3.64 (m, 2H), 2.98 (m, 4H), 2.17 (m, 2H), 1.99 (m, 2H), 1.13 (m, 1H), 0.65 (m, 2H), 0.39 (m, 2H).

出典