反应详情

4-Amino-3-Fluorobenzoic acid (Fluorochem; 1 g, 6.44 mmol), 4-Amino-1-methylpiperidine (Fluorochem; 811 mg, 7.09 mmol), HATU (2.70 g, 7.09 mmol), DIPEA (3.4 mL, 19.32 mmol) and DMF (15 mL) were combined and stirred for 18 hrs at room temperature. The solvent was evaporated and the resultant material dissolved in DCM (with a little MeOH to aid solubility) and chromatographed on silica eluting with a gradient of 0-10% 2M ammonia in MeOH/DCM. Fractions containing product were combined and evaporated to give an orange solid which was dissolved in MeOH and added to a 50 g SCX-2 column pre-wet with MeOH (2 column volumes). The column was flushed with MeOH (2 column volumes) and the product eluted with 2M ammonia in MeOH. Product containing fractions were evaporated to yield the title compound as a beige solid. (1.72 g, 100%)

1. customThe solvent was evaporated
2. dissolutionthe resultant material dissolved in DCM (with a little MeOH to aid solubility) and
3. customchromatographed on silica eluting with a gradient of 0-10% 2M ammonia in MeOH/DCM
4. additionFractions containing product
5. customevaporated
6. customto give an orange solid which
7. customThe column was flushed with MeOH (2 column volumes)
8. washthe product eluted with 2M ammonia in MeOH
9. additionProduct containing fractions
10. customwere evaporated