Triethylamine → HCID 22051110, compound

4-amino-3-bromo-1-(3-fluorobenzyl)pyridin-2(1H)-one (from step 3) (0.30 g, 1.01 mmol) and 4-dimethylaminopyridine (0.002 g, 0.01 mmol) were suspended in acetonitrile (5 mL) followed by dropwise addition of triethylamine (0.2 mL, 1.41 mmol). This reaction mixture was stirred for 10 minutes at room temperature before being cooled to 0° C. 2,6-difluorobenzoyl chloride (0.37 g, 2.12 mmol) was added dropwise and the reaction was heated at reflux overnight. The reaction was cooled to room temperature and 1N NaOH (10 mL) was added. The reaction was then stirred for 45 minutes at room temperature. The reaction mixture was extracted with ethyl acetate (3×25 mL) and the organic layer washed with 1N NaOH (2×25 mL), H2O (until pH neutral), brine (50 mL), dried over MgSO4, concentrated, and subjected to chromatography (on C-18, acetonitrile/H2O with 0.1% trifluoracetic acid) to afford a white solid (0.19 g, 43%). 1H NMR (400 MHz, CDCl3) δ 8.42 (br s, 1H), 7.67 (d, J=7.65 Hz, 1H), 7.49 (app tt, J=6.31, 8.60 Hz, 1H), 7.33-28 (m, 2H), 7.10-6.97 (m, 5H), 5.17 (s, 2H). ES-HRMS m/z 437.0083 (M+H C19H12BrF3N2O2 requires 437.0107).

1. temperaturebefore being cooled to 0° C
2. temperaturethe reaction was heated
3. temperatureat reflux overnight
4. temperatureThe reaction was cooled to room temperature
5. stirringThe reaction was then stirred for 45 minutes at room temperature
6. extractionThe reaction mixture was extracted with ethyl acetate (3×25 mL)
7. washthe organic layer washed with 1N NaOH (2×25 mL), H2O (until pH neutral), brine (50 mL)
8. dry with materialdried over MgSO4
9. concentrationconcentrated

ORD record

ord-ba438fe08ec54400890141e6251d260e

Source dataset

uspto-grants-2006_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07067540B2