Methanol → 6-Bromo-1,2,3,4-tetrahydro-[1,8]naphthyridin-4-ol

Temperature

-78 °C

7-Bromo-1,2,3,4-tetrahydro-[1,8]naphthyridin-4-ol (460 mg) was dissolved in anhydrous tetrahydrofuran (25 mL) and cooled to −78° C. A solution of n-butyllithium in tetrahydrofuran was added (1.6 M, 8.5 mL) (5-7 equiv.) and the reaction was warmed slowly to room temperature. After 2-5 hours, methanol (2 mL) was added and the contents were concentrated to dryness. The residue was dissolved in a mixture of dichloromethane and acetic acid (1:1, v/v, 20 mL) and N-bromosuccinimide (450 mg) (1.2 equiv.) were added. After 45 minutes, the mixture was concentrated to dryness onto silica gel, and purified by silica gel chromatography to give the title compound as yellow solids (25-65% yield). M.p. 125-128° C., LCMS: m/z=229 (M+H+), 1H-NMR (DMSO-d6, 400 MHz) δ 1.72 (m, 2H), 3.25 (m, 2H), 4.56 (m, 1H), 5.33 (d, J=5.0 Hz, 1H), 6.8 (bs, 1H), 7.47 (d, J=2.5 Hz, 1H), 7.87 (d, J=2.5 Hz, 1H).

1. temperaturethe reaction was warmed slowly to room temperature
2. concentrationthe contents were concentrated to dryness
3. additionwere added
4. waitAfter 45 minutes
5. concentrationthe mixture was concentrated to dryness onto silica gel
6. custompurified by silica gel chromatography

ORD record

ord-1b229fb977aa4ef594e4565fc5bec4a7

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08080561B2