1,2-Dibromoethane → 2-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-7-(phenethylthio)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one

Participants

Reaction Conditions

Reaction Steps

A mixture of N-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-4-(phenethylthio)-1H-pyrrole-2-carboxamide (20.0 mg, 0.0450 mmol), 1,2-dibromoethane (20.0 μL, 0.227 mmol), NBu4Br (43.5 mg, 0.135 mmol) and 1N NaOH (0.227 mL, 0.227 mmol) in dichloroethane (0.227 mL) was allowed to stir at 50° C. for 4 h. The reaction mixture was cooled to rt, diluted with EtOAc (20 mL), washed with water (×2, 15 mL), brine, dried over anhydrous Na2SO4, concentrated and purified by preparative HPLC: PHENOMENEX® Luna AXIA 5μ C18 21.2×100 mm, 15 min gradient, 10% MeOH/90% H2O/0.1% TFA to 90% MeOH/10% H2O/0.1% TFA, 5 min hold; 20 mL/min, UV detection at 220 nm, 8.949 min retention time to afford 11.5 mg of the title compound as a light yellow solid: 1H NMR (500 MHz, CDCl3) δ 1.34 (s, 6 H), 2.86-2.91 (m, 2 H), 2.92-2.98 (m, 2 H), 3.83 (s, 2 H), 3.85 (s, 3 H), 4.05-4.11 (m, 2 H), 4.24-4.28 (m, 2 H), 6.78-6.84 (m, 2 H), 6.93 (d, J=8.2 Hz, 1 H), 6.96 (d, J=2.2 Hz, 1 H), 7.07 (s, 1 H), 7.18 (d, 7=8.2 Hz, 2 H), 7.21 (d, 7.1 Hz, 1 H), 7.26-7.32 (m, 2 H); HPLC a) column: PHENOMENEX® Luna 5μ 4.6×50 mm, 4 min gradient, 10% MeOH/90% H2O/0.1% H3PO4 to 90% MeOH/10% H2O/0.1% H3PO4; 1 min hold, 4 mL/min UV detection at 220 nm, 3.470 min retention time, (>95%); HPLC b) column: PHENOMENEX® Luna C18 4.6×50 mm, 4 min gradient, 10% MeOH/90% H2O/0.1% TFA to 90% MeOH/10% H2O/0.1% TFA, 1 min hold; 4 mL/min, UV detection at 220 nm, 3.461 min retention time; MS (ESI) 467 [M+H]+.

Provenance & Evidence