반응 #2148349
ord-243aed57ae684c3db948a3de348b9d36
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시약
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후처리
- 1온도was heated at 100° C. for 2 h
- 2온도Subsequently the reaction was cooled to rt
- 3기타partitioned with EtOAc (30 mL) and 5% aq NaHCO3 (20 mL)
- 4추출The aqueous layer was extracted with fresh EtOAc (2×20 mL)
- 5건조The combined organic layers were dried over magnesium sulfate
- 6여과filtered
- 7기타The crude material was purified by flash column chromatography on silica with DCM/4% MeOH as eluant
실험 절차
To a solution of 3-hydroxy-2,2-dimethylpropanoic acid (88 mg, 0.7 mmol) in DMF (5 mL) were added DIPEA (0.26 mL, 1.5 mmol) and HATU (0.21 g, 0.7 mmol). After stirring at rt for 15 min, 17 (0.25 g, 0.7 mmol) was added as a solution in DMF (2 mL). The reaction was stirred at rt until complete consumption of 17 was determined by LC/MS and then was heated at 100° C. for 2 h. Subsequently the reaction was cooled to rt, partitioned with EtOAc (30 mL) and 5% aq NaHCO3 (20 mL). The aqueous layer was extracted with fresh EtOAc (2×20 mL). The combined organic layers were dried over magnesium sulfate, filtered and reduced to dryness. The crude material was purified by flash column chromatography on silica with DCM/4% MeOH as eluant to give 3-(5-(5-(1-hydroxy-2-methylpropan-2-yl)-1,2,4-oxadiazol-3-ylamino)-2-methylphenyl)-1,7-dimethyl-1,6-naphthyridin-2(1H)-one (A35) as a clear glassy solid. 1H NMR (400 MHz, d6-DMSO) 9.86 (s, 1H), 8.81 (s, 1H), 7.93 (s, 1H), 7.43 (s, 1H), 7.37 (dd, J=8, 2 Hz, 1H), 7.28 (d, J=2 Hz, 1H), 7.21 (d, J=8 Hz, 2H), 5.10 (t, J=5.5 Hz, 1H), 3.65 (s, 3H), 3.55, (d, J=5.5 Hz, 1H) 2.61 (s, 3H), 2.07 (s, 3H), 1.31 (s, 6H). MS m/z 420.4 (M+1).