反应详情

温度

92.5 °C

To a mixture of intermediate 6, cis-3-{[(tert-butoxycarbonyl)(methyl)amino]-methyl}cyclobutyl methanesulfonate (1.59 g, 5.42 mmol), intermediate 23, 2,4-dichloro-3-(pyrrolidin-1-ylmethyl)phenol (2 g, 8.13 mmol), and Cs2CO3 (2.65 g, 8.13 mmol) in DMSO (30 mL) was heated at 90-95° C. for 2 h under vigorous stirring in a flow of argon, and then cooled. Water (20 mL) and ether (50 mL) were added, and the layers were separated. The water layer was subjected to extraction with ether (2×50 mL). The combined organic layers were washed with water (30 mL), brine, dried with Na2SO4, and evaporated. The residue was purified by chromatography (silica gel, 63/100 μm, 50 g, CHCl3/hexane 20:80→100:0, CHCl3/MeOH 100:0→80:20) to furnish the title compound (1.7 g, 70%). LC/MS data: 443.1, 444.1, 445.1 (M+H) (calculated for C22H32Cl2N2O3 443.42). 1H NMR-data (DMSO-d6): 7.35 (d, 1H, J=9 Hz, Ar—H); 6.86 (d, 1H, J=9 Hz, Ar—H); 4.81-4.90 (m, 1H); 3.82 (brs, 2H, CH2); 3.33 (d, 2H, J=8 Hz, CH2); 2.78 (s, 3H, NCH3); 2.50-2.62 (m, 5H); 2.22-2.30 (m, 2H); 2.11-2.21 (m, 2H), 1.58-1.72 (m, 4H); 1.40 (brs, 9H, Boc).

1. temperaturecooled
2. customthe layers were separated
3. extractionThe water layer was subjected to extraction with ether (2×50 mL)
4. washThe combined organic layers were washed with water (30 mL), brine
5. dry with materialdried with Na2SO4
6. customevaporated
7. customThe residue was purified by chromatography (silica gel, 63/100 μm, 50 g, CHCl3/hexane 20:80→100:0, CHCl3/MeOH 100:0→80:20)