Cesium carbonate → US9814704, Example 121

To a solution of 5-(3,4,5-trimethoxyphenyl)-1-((2-(trimethylsilyl)ethoxy)-methyl)-1H-pyrrolo[2,3-b]pyridin-2(3H)-one (Compound BN, 43 mg, 0.10 mmol) in DMF (2 mL) was added cesium carbonate (0.17 g, 0.50 mmol) and 1,4-diiodobutane (13 μL, 0.10 mmol). The resulting solution was stirred for 4 hr at room temperature, after which it was partitioned between EtOAc and H2O. The organic layer was separated, dried over MgSO4, filtered, and concentrated in vacuo. The residue was dissolved in 6 N HCl (10 mL) and MeOH (5 mL), and the resulting mixture was stirred at room temperature overnight, after which it was partitioned between EtOAc and H2O. The organic layer was concentrated in vacuo, and the residue was dissolved in EtOH (2 mL). Potassium acetate (100 mg) was then added, and the reaction was stirred for 2 hr. The resulting solution was purified via preparatory HPLC to give the title compound (18 mg, 51%). 1H NMR (CDCl3, 300 MHz): δ 9.53 (s, 1H), 8.32 (d, J=2.1 Hz, 1H), 7.56 (s, 1H), 6.69 (s, 2H), 3.95 (s, 6H), 3.90 (s, 3H), 2.28 (m, 2H), 2.24 (m, 2H), 1.97 (m, 4H). HPLC retention time: 2.00 minutes; MS ESI (m/z): 355.4 (M+1)+, calc. 354.

1. customafter which it was partitioned between EtOAc and H2O
2. customThe organic layer was separated
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. dissolutionThe residue was dissolved in 6 N HCl (10 mL)
7. stirringMeOH (5 mL), and the resulting mixture was stirred at room temperature overnight
8. customafter which it was partitioned between EtOAc and H2O
9. concentrationThe organic layer was concentrated in vacuo
10. dissolutionthe residue was dissolved in EtOH (2 mL)
11. additionPotassium acetate (100 mg) was then added
12. stirringthe reaction was stirred for 2 hr
13. customThe resulting solution was purified via preparatory HPLC

ORD record

ord-d35b15c0853248fe895479f64dfcb14e

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08846909B2