反应详情

Add oxalyl chloride (0.18 mL, 2.1 mmol) dropwise to a solution of 1-benzylindol-3-carboxylic acid (0.48 g, 1.9 mmol) in pyridine and CH3CN (5 mL each) cooled in an ice bath. Stir the reaction mixture for 2.25 hr. and then add a suspension of 2-amino-6-(1-methylpiperidin-4-ylcarbonyl)pyridine (0.56 g, 1.9 mmol) in CH3CN (5 mL) and pyridine (12 mL). Warm the reaction mixture to room temperature overnight. Quench the reaction with cold H2O (20 mL) and dilute with CHCl3. Adjust the pH to 11 with Na2CO3 and separate the layers. Extract the aqueous layer with CHCl3 (2×30 mL). Combine the organic fractions and dry with anhydrous MgSO4, filter and concentrate the mixture in vacuo. Purify the product by chromatography on a silica gel column, eluting with methanol/CH2Cl2 (5:95) followed by methanol/CH2Cl2 (10:90) to afford the sub-title compound (0.44 g, 51%). 1H NMR (CD3OD) δ 8.45 (d, J=8 Hz, 1H), 8.32 (s, 1H), 8.26 (m, 1H), 7.95 (t, J=8 Hz, 1H), 7.72 (d, J=8 Hz, 1H), 7.45 (m, 1H), 7.22-7.37 (m, 7H), 5.51 (s, 2H), 3.90 (m, 1H), 2.93-3.01 (m, 2H), 2.33 (s, 3H), 2.21-2.31 (m, 2H), 1.92-1.99 (m, 2H), 1.71-1.84 (m, 2H); CIMS (Methane) m/z 453 [C28H28N4O2+H]+.

1. temperaturecooled in an ice bath
2. additionand then add
3. customQuench
4. customthe reaction with cold H2O (20 mL)
5. customseparate the layers
6. extractionExtract the aqueous layer with CHCl3 (2×30 mL)
7. dry with materialCombine the organic fractions and dry with anhydrous MgSO4
8. filtrationfilter
9. concentrationconcentrate the mixture in vacuo
10. customPurify the product by chromatography on a silica gel column
11. washeluting with methanol/CH2Cl2 (5:95)