反应详情

温度

50 °C

Into a 20 mL vial, a solution of Example 149C (51 mg, 0.16 mmol) dissolved in dimethylformamide (0.5 mL) was added, followed by the addition of (S)-(+)-tetrahydrofurfurylamine (18.2 mg, 0.18 mmol) dissolved in dimethylformamide (0.9 mL). A solution of HATU (68 mg, 0.18 mmol) dissolved in dimethylformamide (0.5 mL) was added followed by a solution of diisopropylethylamine (0.087 mL, 0.5 mmol) dissolved in dimethylformamide (0.5 mL). The mixture was shaken at 50° C. overnight. The reaction was filtered through a Si-Carbonate cartridge (6 mL-1 g) supplied by Silicycle Chemical Division, and the filtrate was transferred to 20 mL vials. The reaction was checked by LC/MS and concentrated to dryness. The residue was dissolved in 1:1 DMSO/methanol and purified by reverse phase HPLC (Agilent, 5%-100% TFA/water gradient, 8 minute run). 1H NMR (300 MHz, DMSO-d6/D2O) δ ppm 1.35-1.54 (m, 1H) 1.64-1.96 (m, 3H) 3.17-3.26 (m, 1H) 3.32-3.38 (m, 1H) 3.50-3.77 (m, 2H) 3.81-4.00 (m, 1H) 5.58-5.74 (m, 2H) 7.21-7.41 (m, 5H) 7.54-7.66 (m, 1H) 7.68-7.84 (m, 1H) 8.01-8.19 (m, 2H). MS (ESI−) m/z 401 (M−H)−.

1. additionwas added
2. additionwas added
3. filtrationThe reaction was filtered through a Si-Carbonate cartridge (6 mL-1 g)
4. concentrationconcentrated to dryness
5. dissolutionThe residue was dissolved in 1:1 DMSO/methanol
6. custompurified by reverse phase HPLC (Agilent, 5%-100% TFA/water gradient, 8 minute run)