反应详情

To a solution containing 3-(3-aminopyridin-4-yl)-N-(2-phenylpropan-2-yl)benzamide (1.7 g, 5.1 mmol), triethylamine (5.2 g, 51.3 mmol), and dichloromethane (85 mL) was added methanesulfonylchloride (0.90 mL, 11.3 mmol) in dichloromethane (75 mL) dropwise over 3 min. The solution was maintained at room temperature for 1 h and concentrated to remove all solvent. The residue thus obtained was dissolved in THF (51 mL) and tetrabutylammoniumfluoride (24 mL, 1.0 M in THF) was added in a steady stream via syringe. The solution was maintained at 60° C. for 18 h, concentrated and dissolved in ethyl acetate (75 mL). The solution was washed with water (5×50 mL), washed with brine (50 mL), dried over MgSO4, filtered and concentrated. Purification on silica gel (0-8% methanol/dichloromethane, 60 min gradient) afforded 3-(3-(methylsulfonamido)pyridin-4-yl)-N-(2-phenylpropan-2-yl)benzamide as a pale yellow foam. 1H NMR (500 MHz, DMSO-D6) δ ppm 9.42 (s, 1H), 8.64 (s, 1H), 8.56 (d, J=4.88 Hz, 1H), 8.45 (s, 1H), 8.03 (s, 1H), 7.90 (d, J=7.63 Hz, 1H), 7.71 (d, J=7.63-7.63 Hz, 1H), 7.58 (t, J=7.78 Hz, 1H), 7.49 (d, J=4.88 Hz, 1H), 7.40 (d, J=7.93 Hz, 2H), 7.29 (t, J=7.63 Hz, 2H), 7.17 (t, J=7.17 Hz, 1H), 2.85 (s, 3H), 1.69 (s, 6H). LCMS: retention time: 1.277 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters-Sunfire, 5u, C18, 4.6×50 mm column using a SPD-10AV LTV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 4 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 mM where solvent A was 10% CH3CN/90% H2O/10 mM TFA and solvent B was 10% H2O/90% CH3CN/10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 410 (MH+).

1. concentrationconcentrated
2. customto remove all solvent
3. customThe residue thus obtained
4. temperatureThe solution was maintained at 60° C. for 18 h
5. concentrationconcentrated
6. dissolutiondissolved in ethyl acetate (75 mL)
7. washThe solution was washed with water (5×50 mL)
8. washwashed with brine (50 mL)
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated
12. customPurification on silica gel (0-8% methanol/dichloromethane, 60 min gradient)