反应详情

A mixture of 42 mg of 5-(6-fluoro-1H-benzimidazol-2-yl)-9H-pyrrolo[1,2-a]indol-9-ylamine acetate obtained according to the preceding stage, 19 mg of 1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid (which can be obtained according to WO 2003/000688), 39 mg of o-((ethoxycarbonyl)cyanomethylene-amino)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TOTU) and 16 μl of diisopropylethylamine in 3 ml of N-methylpyrrolidone is stirred in a 100 ml round-bottomed flask. After 1 hour, the reaction medium is evaporated to dryness, the residue is taken up with 30 ml of a saturated solution of sodium bicarbonate and the aqueous phase is extracted with 4 times 30 ml of ethyl acetate. The combined organic phases are washed with 3 times 30 ml of a saturated solution of sodium chloride, dried over magnesium sulphate, and evaporated to dryness under vacuum. The residue is chromatographed on silica gel (15-40 μm), elution being carried out with a gradient of methanol (2% to 5% v/v) in dichloromethane, and then on a second column of silica gel (15-40 μm), elution being carried out with pure ethyl acetate. 12 mg of 1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid [5-(6-fluoro-1H-benzimidazol-2-yl)-9H-pyrrolo[1,2-a]indol-9-yl]amide are obtained in the form of a brown solid, the characteristics of which are the following:

1. customobtained
2. customthe reaction medium is evaporated to dryness
3. extractionthe aqueous phase is extracted with 4 times 30 ml of ethyl acetate
4. washThe combined organic phases are washed with 3 times 30 ml of a saturated solution of sodium chloride
5. dry with materialdried over magnesium sulphate
6. customevaporated to dryness under vacuum
7. customThe residue is chromatographed on silica gel (15-40 μm), elution
8. washon a second column of silica gel (15-40 μm), elution