反应详情

A solution of 3-(5,6-dimethyl-1H-benzoimidazol-2-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine [0.150 g, Example 251(a)] in dimethyl formamide (4 ml) was treated with diisopropylethylamine (0.54 ml) and then with dimethyl carbamyl chloride (0.122 ml). After stirring for 1 hour the reaction mixture was quenched by the addition of methanol (0.1 ml) and then diluted with ethyl acetate. This mixture was washed five times with brine and then evaporated. The residue was treated with tetrahydrofuran (9 ml) and methanol (3 ml) and the resulting solution was then treated with potassium hydroxide (50 mg). This mixture was stirred for 1 hour, then acidified by addition of hydrochloric acid (1M) and then extracted three times with ethyl acetate. The aqueous layer was basified by addition of sodium carbonate and the resulting suspension was filtered, then washed with water, then dried in air and then azeotroped with toluene to yield 3-(5,6-dimethyl-1H-benzoimidazol-2-yl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid isopropylamide as a pale brown solid. MS: 339 (M+H)+. HPLC (METHOD F1): RT=8.67 minutes.

1. customwas quenched by the addition of methanol (0.1 ml)
2. additiondiluted with ethyl acetate
3. washThis mixture was washed five times with brine
4. customevaporated
5. additionThe residue was treated with tetrahydrofuran (9 ml) and methanol (3 ml)
6. additionthe resulting solution was then treated with potassium hydroxide (50 mg)
7. stirringThis mixture was stirred for 1 hour
8. additionacidified by addition of hydrochloric acid (1M)
9. extractionextracted three times with ethyl acetate
10. additionThe aqueous layer was basified by addition of sodium carbonate
11. filtrationthe resulting suspension was filtered
12. washwashed with water
13. customdried in air
14. customazeotroped with toluene