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With N-Bromosuccinimide; In acetonitrile; for 3.5h;Reflux; |
A slurry of the product of Step 4 and NBS (39.747 g, 223.3 mmol) in MeCN (500 mL, anhydrous) was slowly heated to a gentle reflux over a period of approximately 2 h and maintained at a gentle reflux for 1.5 h. (This reaction can be monitored by LC/MS). The reaction mixture was then slowly cooled to room temperature over a period of 3 h and the observed solid was removed by simple filtration. The collected solid was washed with MeCN (100 mL×3) to provide 47 g of the desired product. This material was used in the next step without further purification.1H NMR (400 MHz, CD3OD) δ ppm 7.46(s, 1H), 7.81 (dd, J=8.40, 2.00 Hz, 1H), 7.88 (d, J=8.8 Hz, 1H), 8.27(d, J=2.00 Hz, 1H); 13C NMR (100 MHz, DMSO-D6) δ ppm 96.68, 126.34, 127.58, 127.71, 130.73, 132.20, 133.47, 134.46, 159.88; LC-MS, MS m/z 258 (M++H). |
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With N-Bromosuccinimide; In acetonitrile; at 20.0℃;Reflux; |
Step 5: A slurry of the product of Step 4, Example 2 and NBS (39.747 g, 223.3 mmol) in MeCN (500 mL, anhydrous) was slowly heated to a gentle reflux over a period of approximately 2 h and maintained at a gentle reflux for 1.5 h. (This reaction can be monitored by LC/MS). The reaction mixture was then slowly cooled to room temperature over a period of 3 h and the observed solid was removed by simple filtration. The collected solid was washed with MeCN (100 mL×3) to provide 47 g of the desired product. This material was used in the next step without further purification. 1H NMR (400 MHz, CD3OD) δ ppm 7.46(s, 1H), 7.81 (dd, J=8.40, 2.00 Hz, 1H), 7.88 (d, J=8.8 Hz, 1H), 8.27(d, J=2.00 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ ppm 96.68, 126.34, 127.58, 127.71, 130.73, 132.20, 133.47, 134.46, 159.88; LC-MS, MS m/z 258. |
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With N-Bromosuccinimide; In acetonitrile; at 20.0℃; for 6.5h;Heating / reflux; |
Step 5:; A slurry of the product of Step 4 and NBS (39.747 g, 223.3 mmol) in MeCN (500 mL, anhydrous) was slowly heated to a gentle reflux over a period of approximately 2 h and maintained at a gentle reflux for 1.5 h (This reaction can be monitored by LC/MS). The reaction mixture was then slowly cooled to room temperature over a period of 3 h and the observed solid was removed by simple filtration. The collected solid was washed with MeCN (100 mL×3) to provide 47 g of the desired product. This material was used in the next step without further purification.1H NMR (400 MHz, CD3OD) δ ppm 7.46 (s, 1H), 7.81 (dd, J=8.40, 2.00 Hz, 1H), 7.88 (d, J=8.8 Hz, 1H), 8.27 (d, J=2.00 Hz, 1H); 13C NMR (100 MHz, DMSO-D6) δ ppm 96.68, 126.34, 127.58, 127.71, 130.73, 132.20, 133.47, 134.46, 159.88; LC-MS, MS m/z 258. |