Cesium fluoride → methyl 4-(2-fluoropyridin-4-yl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylate

Temperature

100 °C

1-Tert-butyl 2-methyl 4-chloro-1H-pyrrolo[3,2-c]pyridine-1,2-dicarboxylate (100 mg, 0.322 mmole), 2-fluoro-4-(tributylstannyl)pyridine (162 mg, 0.418 mmole), CsF (108 mg, 0.708 mmole), and bis(tri-t-butylphosphine)palladium(0) (16 mg, 0.031 mmole) were combined in a screw cap vial. To this was added 1,4-dioxane (1 mL). N2 was bubbled through the mixture for 10 seconds. The vial was capped then heated to 100° C. After 6 hr was cooled to RT, diluted with EtOAc, filtered through a pad of Celite washing with EtOAc, and concentrated. The residue was taken up in 2 mL CH2Cl2. To this was added 2 mL TFA. After 2 hr the mixture was concentrated. The residue was taken up in saturated NaHCO3 and extracted with CH2Cl2 (3×). The combined organic layers were dried (MgSO4), filtered, and concentrated. Flash column chromatography (Biotage-SNAP-10 g SiO2, 70% EtOAc/hexanes) gave the title compound (67 mg, 77%) as an off-white solid. 1H NMR (400 MHz, CDCl3): δ 9.23 (bs, 1 H); 8.56 (d, J=5.8 Hz, 1 H); 8.40 (d, J=5.2 Hz, 1 H); 7.82-7.79 (m, 1 H); 7.56 (s, 1 H); 7.50 (dd, J=2.0, 1.1 Hz, 1 H); 7.43 (dd, J=5.8, 1.1 Hz, 1 H); 4.00 (s, 3 H).

1. customcap vial
2. customN2 was bubbled through the mixture for 10 seconds
3. customThe vial was capped
4. temperatureAfter 6 hr was cooled to RT
5. additiondiluted with EtOAc
6. filtrationfiltered through a pad of Celite
7. washwashing with EtOAc
8. concentrationconcentrated
9. additionTo this was added 2 mL TFA
10. concentrationAfter 2 hr the mixture was concentrated
11. extractionextracted with CH2Cl2 (3×)
12. dry with materialThe combined organic layers were dried (MgSO4)
13. filtrationfiltered
14. concentrationconcentrated

ORD record

ord-8cbfd12dd1c3428180e4299ead8cb923

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09102673B2