反应详情

In 10 ml of dry DCM, 0.5 mmol of (R)-2-(3-oxo-1-tosyl-1,2,3,4-tetrahydropyrazin-2-yl)acetic acid and 0.5 mmol of PyClU were combined. Next, 0.6 mmol of (R)—N-methyl-6-(piperidin-1-ylmethyl)-1,2,3,4-tetrahydronaphthalen-1-amine (prepared in Example 11) and 1.5 mmol of DIEA were added and the mix was stirred at room temperature under nitrogen for 1 h. The reaction was then quenched with 20 ml of saturated sodium bicarbonate, then extracted with EtOAc (2×30 ml), washed with brine (1×20 ml), dried with sodium sulfate, and concentrated. Purification by chomatography over silica gel using 0 to 15% MeOH (2M ammonia) in ethyl acetate gave the title compound. MS 551 (ESI, pos. ion). Similarly, N-methyl-2-((R)-3-oxo-1-(phenylsulfonyl)-1,2,3,4-tetrahydropyrazin-2-yl)-N—((R)-6-(piperidin-1-ylmethyl)-1,2,3,4-tetrahydronaphthalen-1-yl)acetamide, N-methyl-2-((R)-3-oxo-1-tosyl-1,2,3,4-tetrahydropyrazin-2-yl)-N—((R)-7-(piperidin-1-ylmethyl)choman-4-yl)acetamide, N-methyl-2-((R)-3-oxo-1-(phenylsulfonyl)-1,2,3,4-tetrahydropyrazin-2-yl)-N—((R)-7-(piperidin-1-ylmethyl)choman-4-yl)acetamide, N—((R)-7-((tert-butylamino)methyl)choman-4-yl)-N-methyl-2-((R)-3-oxo-1-tosyl-1,2,3,4-tetrahydropyrazin-2-yl)acetamide, and N—((R)-6-((tert-butylamino)methyl)-1,2,3,4-tetrahydronaphthalen-1-yl)-N-methyl-2-((R)-3-oxo-1-tosyl-1,2,3,4-tetrahydropyrazin-2-yl)acetamide were prepared.

1. customThe reaction was then quenched with 20 ml of saturated sodium bicarbonate
2. extractionextracted with EtOAc (2×30 ml)
3. washwashed with brine (1×20 ml)
4. dry with materialdried with sodium sulfate
5. concentrationconcentrated
6. customPurification by chomatography over silica gel using 0 to 15% MeOH (2M ammonia) in ethyl acetate