反应详情

To a solution of 5-cyclopropyl-2-(4-(2-methyl-5-(1,2,3,6-tetrahydropyridin-4-yl)-2,3-dihydrobenzofuran-2-yl)piperidin-1-yl)pyrimidine (90 mg, 0.216 mmol) and triethylamine (0.061 mL, 0.432 mmol) in CH2Cl2 (2 mL) at 0° C. was added methyl 4-(chlorosulfonyl)butanoate (65 mg, 0.324 mmol). Upon completion of addition, the reaction mixture was warmed to room temperature, where it stirred for 3 h. After this time, the reaction mixture was diluted with CH2Cl2 (4 mL), and the resulting mixture was washed with aqueous NaHCO3 (saturated, 3×3 mL). The organic layer was separated, dried (Na2SO4), filtered, and concentrated to yield a residue. The residue was purified via preparative HPLC (solvent A: 10% MeOH/H2O with 0.1% TFA; solvent B: 90% MeOH/H2O with 0.1% TFA; Column: PHENOMENEX® Axia 5μ C18 30×100 mm, flow rate=40 mL/min) to afford Compound 11H as a white solid (46 mg, 0.079 mmol, 36.7% yield). 1H NMR (500 MHz, CDCl3) δ ppm 8.02 (s, 2 H), 7.06 (s, 1 H), 7.01-7.05 (m, 1 H), 6.60 (d, J=8.3 Hz, 1 H), 5.82 (ddd, J=3.2, 1.9, 1.7 Hz, 1 H), 4.65-4.78 (m, 2 H), 3.85-3.92 (m, 2 H), 3.60 (s, 3 H), 3.46 (t, J=5.8 Hz, 2 H), 3.08 (d, J=15.7 Hz, 1 H), 2.98 (dd, J=8.4, 6.7 Hz, 2 H), 2.65-2.78 (m, 3 H), 2.50 (d, J=1.7 Hz, 2 H), 2.44 (t, J=7.0 Hz, 2 H), 2.01-2.13 (m, 2 H), 1.76-1.87 (m, 2 H), 1.67-1.75 (m, 1 H), 1.56-1.65 (m, 1 H), 1.30 (s, 3 H), 1.15-1.28 (m, 2 H), 0.76-0.83 (m, 2 H), 0.45-0.51 (m, 2 H). LC/MS (m/z)=581 (M+H)+.

1. additionUpon completion of addition
2. washthe resulting mixture was washed with aqueous NaHCO3 (saturated, 3×3 mL)
3. customThe organic layer was separated
4. dry with materialdried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated
7. customto yield a residue
8. customThe residue was purified via preparative HPLC (solvent A: 10% MeOH/H2O with 0.1% TFA; solvent B: 90% MeOH/H2O with 0.1% TFA; Column: PHENOMENEX® Axia 5μ C18 30×100 mm, flow rate=40 mL/min)