These common heterocyclic compound, 399-94-0, name is 1-Bromo-2,5-difluorobenzene, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. Safety of 1-Bromo-2,5-difluorobenzene
Example 3 3 -((2.5 -difluorophenyl)ethynyl)-5 -( 1 -(piperidin-4-yl)- 1 H-pyrazol-4-yl)- 1 H- pyrrolor2,3-b1pyridine Step 1) tert-butyl 4-(4-(3-((2.5-difluorophenyl ethvnyl -lH-pyrrolor2.3-b1pyridin-5-yl -lH- pyrazol- 1 -yPpiperidine- 1 -carboxylate To a microwave vial was added tert-butyl 4-(4-(3-ethynyl-lH-pyrrolo[2,3-b] pyridin-5-yl)-lH- pyrazol-l-yl)piperidine-l -carboxylate (0.1 g, 0.26 mmol), 2-bromo-l,4-difluorobenzene (58 mg, 0.26 mmol), Pd(PPh3)2Cl2 (9.0 mg, 0.013 mmol), Cul (2.0 mg, 0.013 mmol), Et3N (1 mL), and DMF (4 mL). The mixture was degassed and charged with nitrogen for three times. The vial was capped and then stirred and heated under microwave conditions at 120 C for 30 minutes. Then the mixture was cooled to rt, diluted with DCM (100 mL), and washed with brine (100 mL x 3). The separated organic phase was dried over anhydrous Na2S04 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (v/v) = 1/2) to give the title compound as a light yellow solid (0.14 g, 81%). MS (ESI, pos. ion) m/z: 504.2 (M+l); ‘HNMR: (400 Hz, DMSO-i): delta 1.43 (s, 9H), 1.84 (m, 2H), 2.05 (m, 2H), 2.95 (s, 2H), 4.06 (m, 2H), 4.38 (m, IH), 7.31 (m, IH), 7.38 (m, IH), 7.62 (m, IH), 7.98 (d, J=2.8 Hz, IH), 8.02 (s, IH), 8.19 (d, J=1.8 Hz, IH), 8.41 (s, IH), 8.62 (d, J=1.8 Hz, IH), 12.26 (s, IH).
The synthetic route of 1-Bromo-2,5-difluorobenzene has been constantly updated, and we look forward to future research findings.
Reference:
Patent; CALITOR SCIENCES, LLC; SUNSHINE LAKE PHARMA CO., LTD.; XI, Ning; LI, Xiaobo; ZHOU, Shiqing; WO2014/89280; (2014); A1;,
Bromide – Wikipedia,
bromide – Wiktionary