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Dry 10percent Pd/C(2.48 g) was placed in a 5 L flask under N2. A solution of 2-(benzyloxy)-5-fluorobenzonitrile (148 g, 651 mmol) in methanol (2.34 L) was added slowly under N2. The air of the flask was removed by vacuum and the flask was charged with H2 (balloon) three times. The mixture was stirred at room temperature for 1 hour. The above process was repeated two more times to push the reaction to completion. The mixture was stirred at room temperature for another 2 hours. The mixture was filtered through a Celite pad under N2 and washed with EtOAc (150 mL x 2). The palladium waste was rinsed with water (50 mL) and discarded. The filtrates were concentrated to give (94.6 g, 106 percent) of the desired compound as a yellow solid. MS (APCI -) m/z 137 (M-I) was detected. 1H NMR (400 MHz, DMSOd6) δ 11.07 (br, IH), 7.58 (dd, IH, J= 3.2 Hz, J = 8.2 Hz), 7.43 (m, IH), 6.91-7.03 (dd, IH J = 4.5 Hz, J = 9.2 Hz).
In a 12 L, 4- neck round bottom flask equipped with a mechanic stirrer and temperature probe, a <n="47"/>suspension of sodium hydride (74 g, 1.82 mol) in DMF (1.95 L) was added benzyl alcohol (142 g, 1.3 mol) through a dropping funnel slowly over 30 minutes in an ice bath under nitrogen. The mixture was stirred in an ice bath (0 0C) for 120 minutes, a solution of 2,5- difluorobenzonitrile (180 g, 1.3 mol) in DMF (650 mL) was added through a dropping funnel over 35 minutes. The resulting mixture was warmed up to room temperature. After 2 hours, the mixture was cooled in an ice bath (4 0C) and quenched with saturated NH4Cl (130 mL) followed by the addition of water (2.6 L x 3). The slurry was stirred at room temperature overnight and the precipitate was filtered and washed with water (650 mL x 3). The solid was dried in vacuum for 2 days to give 292 g (99.3 %) of the desired compound. 1H NMR (400 MHz, DMSO-de) delta 7.78 (dd, IH, J = 3.2 Hz, J = 8.2 Hz), 7.5-7.76 (m, IH), 7.35-7.48 (m, 6H), 5.28 (s, 2H).
With hydrogen;palladium 10% on activated carbon; In methanol; at 20℃; for 3h;
Dry 10% Pd/C(2.48 g) was placed in a 5 L flask under N2. A solution of <strong>[945614-14-2]2-(benzyloxy)-5-fluorobenzonitrile</strong> (148 g, 651 mmol) in methanol (2.34 L) was added slowly under N2. The air of the flask was removed by vacuum and the flask was charged with H2 (balloon) three times. The mixture was stirred at room temperature for 1 hour. The above process was repeated two more times to push the reaction to completion. The mixture was stirred at room temperature for another 2 hours. The mixture was filtered through a Celite pad under N2 and washed with EtOAc (150 mL x 2). The palladium waste was rinsed with water (50 mL) and discarded. The filtrates were concentrated to give (94.6 g, 106 %) of the desired compound as a yellow solid. MS (APCI -) m/z 137 (M-I) was detected. 1H NMR (400 MHz, DMSOd6) delta 11.07 (br, IH), 7.58 (dd, IH, J= 3.2 Hz, J = 8.2 Hz), 7.43 (m, IH), 6.91-7.03 (dd, IH J = 4.5 Hz, J = 9.2 Hz).
With dihydrogen peroxide; potassium carbonate; In water; dimethyl sulfoxide; at 0 - 25℃; for 0.5h;
General procedure: A stirred solution of 2-fluoro-benzonitrile (0.88 g) and K2CO3 (0.15 g) in DMSO (3 mL), cooled in an ice bath, was added 35% H2O2 (1 mL). The mixture was allowed to warm up to 25 C for 30 min, poured into H2O (50 mL), and the resulting solid was collected and washed with Et2O to give 23b as white solid: mp 109-111 C (lit.7 116-119C); 1H NMR (400 MHz, Acetone-d6) delta: 7.91 (td, J = 7.7, 1.8 Hz, 1H), 7.57 (tdd, J = 7.2, 5.2, 1.9 Hz, 1H), 7.30 (tt, J = 6.2, 3.1 Hz, 1H), 7.24 (dd, J = 11.5, 8.3 Hz, 1H).
ethyl 5-(1-(2-((R)-2-((tert-butoxycarbonyl)amino)propoxy)-5-fluorophenyl)-2-azabicyclo[3.1.0]hexan-2-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate[ No CAS ]
5-(1-(2-((R)-2-((tert-butoxycarbonyl)amino)propoxy)-5-fluorophenyl)-2-azabicyclo[3.1.0]hexan-2-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid[ No CAS ]