Sodium Bicarbonate → tert-Butyl ((6-(7-chlorothieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl)(2-methoxyethyl)carbamate

To a solution of 7-chlorothieno[3,2-b]pyridine (6) (8.84 g, 52.1 mmol) in THF (100 mL) at −78° C. was added n-butyllithium (20.86 mL, 52.1 mmol). After 30 min, zinc chloride (52.1 mL, 52.1 mmol) (1M in ether) was added at −78° C. and the reaction mixture was allowed to warm to r.t. After 1 h, palladium tetrakistriphenylphosphine (1.004 g, 0.869 mmol) and tert-butyl(6-bromopyridin-3-yl)methyl(2-methoxyethyl)carbamate (10) (6 g, 17.38 mmol) in THF (25.00 mL) were added and the mixture was heated to reflux for 1 h and cooled to room temperature. To the cooled reaction mixture were added NaHCO3 (sat. aq.) (100 mL) and EtOAc (100 mL). The organic layer was collected and the aqueous layer was extracted with EtOAc (3×100 mL). The combined organic solutions were washed with brine, dried over anhydrous Na2SO4 and evaporated under reduce pressure. The residue was purified by flash column chromatography (eluent hexane/EtOAc: 5/5, 3/7, 0/100), to afford intermediate 11 (5.41 g, 72% yield). MS (m/z): 434.2 (M+H). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.65 (d, J=5.1 Hz, 1H), 8.52 (d, J=1.6 Hz, 1H), 8.39 (s, 1H), 8.27 (d, J=8.0 Hz, 1H), 7.80 (dd, J=8.1, 2.1 Hz, 1H), 7.58 (d, J=5.1 Hz, 1H), 4.48 (s, 2H), 3.43-3.35 (m, 4H), 3.22 (s, 3H), 1.43-1.33 (m, 9H).

1. waitAfter 1 h
2. temperaturethe mixture was heated
3. temperatureto reflux for 1 h
4. temperaturecooled to room temperature
5. customTo the cooled reaction mixture
6. customThe organic layer was collected
7. extractionthe aqueous layer was extracted with EtOAc (3×100 mL)
8. washThe combined organic solutions were washed with brine
9. dry with materialdried over anhydrous Na2SO4
10. customevaporated
11. customThe residue was purified by flash column chromatography (eluent hexane/EtOAc: 5/5, 3/7, 0/100)

ORD record

ord-5446deff96994701a0c03971684d391f

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09018378B2