反应详情

温度

65 °C

A mixture of 6-bromo-2-[2-(2-(R)-methyl-pyrrolidin-1-yl)-ethyl]-benzothiazole (0.3 g, 0.9 mmol), 3-pyridinyl boronic acid (0.17 g, 1.4 mmol) and 2-(dicyclohexylphosphino)biphenyl (65 mg, 0.2 mmol) in 15 mL of IPA was purged wth nitrogen. Dichlorobis(triphenylphosphine)palladium II (65 mg, 0.1 mmol) was added. Sodium carbonate (0.15 g, 1.35 mmol) was dissolved in 5 g of water, purged with nitrogen, and added to the above mixture. The mixture was heated to 65° C. under nitrogen for 16 hr. After cooling to room temperature 20 mL of methylene chloride was added and the solid was filtered off. The filtrate was concentrated to oil and dissolved in 10 mL of 2N HCl. The acidic aqueous layer was washed with 10 mL methylene chloride, the pH adjusted with 4N NaOH to pH 10, and the product free base was extracted with 20 mL methylene chloride. The methylene chloride layer was concentrated to dryness and purified by column chromatography (silica gel, 10:90 MeOH:CHCl3) to give the pure 2-[2-(2-Methyl-pyrrolidin-1-yl)-ethyl]-6-pyridin-3-yl-benzothiazole (0.2 g, 67% yield). 1H NMR (CDCl3, 400 MHz) δ 1.14 (d, 3H, J=8 Hz), 1.42–1.51 (m, 1H), 1.71–1.86 (m, 2H), 1.92–2.00 (m, 1H), 2.27 (q, 1H, J=8 Hz), 2.41–2.48 (m, 1H), 2.60–2.67 (m, 1H), 3.22–3.37 (m, 4H), 7.36–7.39 (m, 1H), 7.64 (broad d, 1H, J=8 Hz), 7.90 (broad d, 1H, J=8 Hz), 8.03–8.05 (m, 2H), 8.60 (d, 1H, J=4 Hz), 8.89 (d, 1H, J=1.5 Hz); 13C NMR (CDCl3, 400 MHz) δ 19.3, 22.2, 33.0, 34.0, 52.7, 53.8, 59.9, 119.7, 122.6, 123.3, 125.0, 134.2, 135.9, 136.2, 148.0, 148.1, 152.3, 170.7; (DCI/NH3) m/z 324 (M+H)+.

1. customwas purged wth nitrogen
2. custompurged with nitrogen
3. additionadded to the above mixture
4. temperatureAfter cooling to room temperature 20 mL of methylene chloride
5. additionwas added
6. filtrationthe solid was filtered off
7. concentrationThe filtrate was concentrated to oil
8. dissolutiondissolved in 10 mL of 2N HCl
9. washThe acidic aqueous layer was washed with 10 mL methylene chloride
10. extractionthe product free base was extracted with 20 mL methylene chloride
11. concentrationThe methylene chloride layer was concentrated to dryness
12. custompurified by column chromatography (silica gel, 10:90 MeOH:CHCl3)