Tetrahydrofuran → HCID 118061539, Verbindung

Temperatur

70 °C

A stirred solution of Intermediate 241B (18.34 mg, 0.102 mmol) in toluene (1 mL) at RT under nitrogen was added TEA (0.043 mL, 0.305 mmol), DPPA (0.047 mL, 0.204 mmol) and the reaction mixture was heated at 70° C. for 2 h. The reaction mass was cooled to RT and to it was added a solution of Intermediate 185B (30 mg, 0.102 mmol) in THF (1 mL) and stirred for 16 h. The reaction mass was diluted with ethyl acetate (5 mL) and the organic layer was separated. The organic layer was washed sequentially with an aqueous solution of 10% NaHCO3, water, and brine, then dried over Na2SO4, filtered and the filtrate concentrated under reduced pressure. The crude product was purified by preparative HPLC to afford Compound 241 as pale yellow solid (10 mg, 20% yield). The HPLC Retention times are 1.453 min. and 1.467 min. (Methods J and K respectively); MS(ES): m/z=472.2[M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.85 (dd, J=7.28, 2.13 Hz, 1H), 7.69 (ddd, J=8.63, 4.80, 2.13 Hz, 1H), 7.39-7.52 (m, 1H), 7.11-7.33 (2bs, 2H), 7.10 (d, J=7.34 Hz, 1H), 6.36-6.88 (m, 1H), 4.73 (s, 2H), 4.13 (t, J=5.27 Hz, 2H), 3.72-3.99 (m, 5H), 2.00-2.16 (m, 1H), 1.68-1.94 (m, 2H), 1.33-1.53 (m, 1H).

1. temperatureThe reaction mass was cooled to RT and to it
2. customthe organic layer was separated
3. washThe organic layer was washed sequentially with an aqueous solution of 10% NaHCO3, water, and brine
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationthe filtrate concentrated under reduced pressure
7. customThe crude product was purified by preparative HPLC

ORD-Eintrag

ord-e925641210974c84a1e3e5788fd73bf5

Quelldatensatz

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09273058B2