Triethylamine → HCID 135771845, Verbindung

At −70° C., triethylamine (215 μL, 1.54 mmol) was added to a solution of (R)-2-(4-(3-aminopyrrolidin-1-yl)-6-fluoroquinazolin-2-yl)phenol (250 mg, 0.77 mmol) in CH2Cl2 (2.5 mL), followed by the dropwise addition of isobutyl chloroformate (100 μL, 0.77 mmol). The reaction was stirred for 30 minutes and warmed to RT. The mixture was quenched with H2O and extracted with CH2Cl2. The combined organic extracts were dried over MgSO4, filtered, and concentrated. Purification via silica gel chromatography using 2.5-10% EtOAc in a 1:1 mixture of CH2Cl2 and hexanes gave (R)-isobutyl 1-(6-fluoro-2-(2-hydroxyphenyl)quinazolin-4-yl)pyrrolidin-3-ylcarbamate (compound 15) (195 mg, 60%). 1H NMR (400 MHz, acetic acid-d4) δ 8.43 (m, 1H), 8.01 (m, 1H), 7.90 (m, 1H), 7.76 (m, 1H), 7.58 (d, J=5.6 Hz, 1H), 7.37 (m, 1H), 6.93 (m, 2H), 4.07 (m, 5H), 3.75 (d, J=6.2 Hz, 2H), 2.23 (m, 1H), 2.03 (m, 1H), 1.83 (m, 1H), 0.88 (d, J=6.5 Hz, 6H) ppm. LC/MS: m/z 425.3 (M+H)+ at 2.77 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).