反应详情

温度

0 °C

Dissolve 2-chloro-4-fluoro-N-((2R,4R)-3-(2-methyl-piperidin-4-ylamino)-phenyl)-benzamide hydrochloride (Example 41, 30 mg, 0.075 mmol) in methanol (5 mL). Add acetic acid (13 μL, 0.225 mmol) followed by sodium cyanoborohydride (7.1 mg, 0.113 mmol). Cool to 0° C. and add 37% formaldehyde (6.7 μL, 0.083 mmol). Warm to room temperature and stir for 18 hr. Add aqueous saturated sodium bicarbonate and dichloromethane. Separate organic layer and extract aqueous with dichloromethane (2×25 mL). Combine organic extracts, dry (MgSO4), filter, and concentrate in vacuo. Purify by column chromatography (0%–10% 2M NH3 in methanol/CH2Cl2) to yield an oil. Make the hydrochloride salt by sonication with one equivalent of ammonium chloride dissolved in methanol to yield 21 mg (68%) of the title compound. Mass spectrum (ion spray): m/z=376.4 (M+1); mp 159–62° C.

1. temperatureWarm to room temperature
2. extractionSeparate organic layer and extract aqueous with dichloromethane (2×25 mL)
3. dry with materialCombine organic extracts, dry (MgSO4)
4. filtrationfilter
5. concentrationconcentrate in vacuo
6. customPurify by column chromatography (0%–10% 2M NH3 in methanol/CH2Cl2)
7. customto yield an oil