2-Bromoethanol → HCID 71766520, compound

Temperature

85 °C

To a solution of Compound (1) (300 mg, 0.75 mmol) in ACN (6 mL) was added potassium carbonate (311 mg, 2.25 mmol) followed by 2-bromoethanol (91.8 μL, 1.30 mmol). The mixture was heated at 85° C. (a thick precipitate was observed after 10 min) and stirred overnight. More potassium carbonate (300 mg, 2.17 mmol) and 2-bromoethanol (90 μL, 1.27 mmol) were added and the mixture was stirred at 90° C. for another 24 hr. The mixture was cooled to RT and the volatiles were removed in vacuo. The residue was suspended in EtOAc (10 mL) and the organics washed with water (10 mL), brine (10 mL) and dried (MgSO4). The volatiles were removed in vacuo and approximately one sixth of the residue was subjected to column chromatography on silica gel eluting with MeOH:DCM (gradient elution, 0% to 10%) to give partially purified material (50 mg). This material was purified further by column chromatography using C18-reverse phase preparative LCMS eluting with ACN:0.1% formic acid in water (gradient elution, 5% to 100% v/v) to give Compound (2) (7.23 mg). ESI-MS m/z calculated for [M+H]+: 444.2; found: 444.2. 1H NMR (400 MHz, CDCl3) δ 8.51-8.43 (m, 1H), 8.36 (d, J=0.8 Hz, 1H), 7.82-7.71 (m, 3H), 7.51 (s, 1H), 4.11 (dt, J=11.9, 5.6 Hz, 1H), 3.82-3.76 (m, 2H), 3.76-3.67 (m, 1H), 3.18 (s, 3H), 3.05 (d, J=4.8 Hz, 3H), 2.47 (s, 3H), 2.30 (tt, J=8.3, 5.6 Hz, 1H), 1.06-0.96 (m, 2H), 0.96-0.87 (m, 1H), 0.54-0.41 (m, 1H).

1. stirringthe mixture was stirred at 90° C. for another 24 hr
2. temperatureThe mixture was cooled to RT
3. customthe volatiles were removed in vacuo
4. washthe organics washed with water (10 mL), brine (10 mL)
5. dry with materialdried (MgSO4)
6. customThe volatiles were removed in vacuo and approximately one sixth of the residue

ORD record

ord-08d8d0cfd934430bb77d8f82937cf287

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365554B2