60% |
With trichlorophosphate; In N,N-dimethyl-formamide; at 130.0℃; for 12.0h; |
To a mixture of 8-bromoquinazoline-2,4(lH,3H)-dione (12.1 g, 50 mmol, 1 eq.) in POCl3(130 mL) was added DMF (0.5 mL). The mixture was stirred at 130 C for 12 h, then cooled to r.t. and concentrated. The resulting residue was dissolved in EA (100 mL) and poured into ice-water with vigorous stirring. The organic phase was separated and washed with brine, dried over anhydrous Na2S04and concentrated. The resulting residue was purified via column chromatography (PE/EA==10: 1, v/v) to afford 8-bromo-2,4- dichloroquinazoline as a yellow solid (9.1 g, 60% yield). |
60% |
With trichlorophosphate; In N,N-dimethyl-formamide; at 130.0℃; for 12.0h; |
[0287] To a mixture of <strong>[331646-99-2]8-bromoquinazoline-2,4(1H,3H)-dione</strong> (12.1 g, 50 mmol, 1 eq.) in POC13 (130 mL) was added DMF (0.5 mL). The mixture was stirred at 130 C for 12 h, then cooled to r.t. and concentrated. The resulting residue was dissolved in EA (100 mL) and poured into ice-water with vigorous stirring. The organic phase was separated and washed with brine, dried over anhydrous Na2 SO4 and concentrated. The resulting residue was purified via column chromatography (PE/EA==10:1, v/v) to afford 8-bromo-2,4- dichloroquinazoline as a yellow solid (9.1 g, 60% yield). |
0.377 g |
With trichlorophosphate; at 100.0℃; |
Step B: Phosphorus(V) oxy chloride (4.8 mL, 51.86 mmol, 25.0 eq.) was slowly added to a flask containing 8-bromoquinazoline-2,4(lH,3H)-dione (0.500 g, 2.07 mmol, 1.0 eq.). The mixture was heated to 100 C and the progress of the reaction was monitored by TLC analysis (hexanes/EtOAc 2: 1 v/v). Upon complete consumption of the starting material, the reaction mixture was cooled to room temperature and transferred portionwise to an Erlenmeyer flask containing crushed ice with the aid of CH2CI2. The resulting mixture was stirred for 20 min and then extracted with CH2CI2. The organic phases were combined, washed with saturated aqueous NaHCCb (3x40 mL), brine, dried over Na2SC>4, and concentrated in vacuo. The crude solid was purified by silica gel chromatography to provide 8- bromo-2,4-dichloroquinazoline (0.377 g, 65% yield). XH NMR (400 MHz, CDC13) delta 8.29 (d, J= 7.6 Hz, 1H), 8.26 (d, J= 8.4 Hz, 1H), 7.60 (t, J= 8.1 Hz, 1H). MS (ESI) m/z = 275.00 (M+H)+. LCMS Ret time (UV 214/254): 1.511 min. |