Diisopropylethylamine → HCID 44199456, compound

Participants

Reaction Steps

To a solution of (R)-2-(tert-butyldimethylsilyloxy)-3-methylbutanoic acid (83 mg, 0.35 mmol) in DMF (2 mL) were added DIPEA (52 μL, 0.3 mmol) and HATU (0.11 g, 0.3 mmol). After stirring at rt for 15 min, 17 (0.10 g, 0.3 mmol) was added as a solution in DMF (1 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 1 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 dissolved in THF and was added TBAF (2.7 mL of a 1.0 M solution in THF). The mixture was stirred at rt for 2 h. Subsequently the reaction was diluted with EtOAc (20 mL) and washed with water and brine. The organic layer was dried over magnesium sulfate, filtered and reduced to dryness. The crude product was purified by preparative LCMS to give (R)-3-(5-(5-(1-hydroxy-2-methylpropyl)-1,2,4-oxadiazol-3-ylamino)-2-methylphenyl)-1,7-dimethyl-1,6-naphthyridin-2(1H)-one (A92). 1H NMR (400 MHz, d6-DMSO) δ 9.87 (s, 1H), 8.81 (s, 1H), 7.94 (s, 1H), 7.43 (s, 1H), 7.39 (dd, J=8, 2 Hz, 1H), 7.30 (d, J=2 Hz, 1H), 7.21 (d, J=8 Hz, 1H), 6.02 (d, J=6 Hz, 1H), 4.48 (bt, J=6 Hz, 1H), 3.67 (s, 3H), 2.61 (s, 3H), 2.07 (s, 3H) 0.94 (d, J=6 Hz, 3H), 0.87 (d, J=6 Hz, 3H). MS m/z 420.4 (M+1).

Provenance & Evidence