Triethylamine → HCID 90019290, compound

Participants

Reaction Conditions

Reaction Steps

To a suspension of 5-(5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl)pyridine-3-sulfonamide (1) (0.150 g, 0.320 mmol) in CHCl3 (10 mL) was added triethylamine (0.268 mL, 1.92 mmol) followed by 4-dimethylaminopyridine (7.8 mg, 0.064 mmol) under nitrogen atmosphere. The reaction mixture was stirred at 0° C. for 5 min and diethyl phosphorochloridate (0.331 g, 1.92 mmol) was added dropwise. The reaction mixture was allowed to warm up to room temperature and stirred overnight. The reaction mixture was diluted with DCM (20 mL) and water (20 mL), and extracted with DCM (3×50 mL). The combined organic layers were washed with water and brine and dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by HPLC purification to afford ethyl hydrogen diethoxyphosphoryl((5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)quinazolin-2-yl)pyridin-3-yl)sulfonyl)phosphoramidate (9) (0.045 g, 0.063 mmol, 20% yield) as a yellow solid. Preparative (Water mass) HPLC Conditions: Column: Atlantis dc18 (19×250 mm) 10 μm, Mobile Phase A: 10 mm ammonium acetate. Mobile Phase B: acetonitrile, Gradient: 10 to 60% B over 10 min, Flow Rate: 15 mL/min., Retention time: 11.35 min.; 1H NMR (400 MHz, chloroform-d) (δ ppm) 1.20-1.34 (m, 9H) 4.06-4.22 (m, 6H) 4.60-4.77 (m, 2H) 6.63 (br. s., 1H) 7.09-7.20 (m, 3H), 7.44-7.54 (m, 5H) 7.61-7.72 (m, 2H) 7.85-7.96 (m, 1H) 8.42 (d, J=4.02 Hz, 1H) 9.21 (dd, J=6.78, 2.01 Hz, 2H) 9.67 (d, J=2.01 Hz, 1H); LCMS Method D: retention time 1.56 min, [M+l]=713.2.

Provenance & Evidence