Triethylamine → 3-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}-7-(3-pyridinyl)isoquinoline

Temperature

0 °C

The product from Example 63A (0.25 g, 1.0 mmol) and triethylamine (0.15 g, 1.5 mmol) in methylene chloride (10 mL) at −5° C. were treated with methanesulfonyl chloride (0.12 g, 1.2 mmol) and stirred at 0° C. for 2 hours and then stirred at room temperature for 15 hours. The mixture was concentrated under reduced pressure and the residue was treated with K2CO3 (0.21 g, 1.5 mmol) and (2R)-2-methylpyrrolidine (0.13 g, 1.5 mmol) in acetonitrile (15 mL), and then heated at 60° C. for 5 hours. The mixture was concentrated under reduced pressure and the residue was dissolved in 30 mL methylene chloride, washed with 10 mL 15% NaCl, and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 10:90:1 MeOH:CHCl3:Et3N) to provide the title compound. 1H NMR (CDCl3, 400 MHz) δ 9.27 (s, 1H), 8.95 (m, 1H), 8.64 (dd, J=2, 4 Hz, 1H), 8.12 (s, 1H), 7.98 (m, 1H), 1.90-1.86 (m, 2H), 7.56 (s, 1H), 7.44-7.40 (m, 1H), 3.37-3.28 (m, 2H), 3.26-3.18(m, 2H), 2.68-2.61(m, 2H), 2.51-2.46(m, 1H), 2.38-2.31 (m, 1H), 2.00-1.93(m, 1H), 1.88-1.82(m, 1H), 1.80-1.72(m, 1H), 1.55-1.46 (m, 1H), 1.14(d, 3H); 13C NMR (CDCl3, 400 MHz) δ 9.27 153.8, 151.9, 148.4, 147.9, 135.6, 135.5, 135.4, 134.1, 129.1, 127.0, 126.9, 125.2, 123.4, 118.2, 60.4, 54.1, 54.0, 37.2, 32.8, 21.9, 19.0.

1. stirringstirred at room temperature for 15 hours
2. concentrationThe mixture was concentrated under reduced pressure
3. temperatureheated at 60° C. for 5 hours
4. concentrationThe mixture was concentrated under reduced pressure
5. dissolutionthe residue was dissolved in 30 mL methylene chloride
6. washwashed with 10 mL 15% NaCl
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by column chromatography (silica gel, 10:90:1 MeOH:CHCl3:Et3N)

ORD record

ord-8bd9ce897c094d89b45ab4da502949f3

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07456196B2