[CH3:1][O:2][C:3]([C:5]1[O:9][N:8]=[C:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:6]=1[C:16]([OH:18])=O)=[O:4].Cl.CN.C1C=CC2N(O)N=[N:28][C:26]=2C=1.C(Cl)CCl.C(N(C(C)C)CC)(C)C>CN(C=O)C>[CH3:26][NH:28][C:16]([C:6]1[C:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:8][O:9][C:5]=1[C:3]([O:2][CH3:1])=[O:4])=[O:18]
A mixture of 5-(methoxycarbonyl)-3-phenylisoxazole-4-carboxylic acid (50 mg, 0.202 mmol), methylamine hydrochloride (19.12 mg, 0.283 mmol), HOBT (37.2 mg, 0.243 mmol), EDC (46.5 mg, 0.243 mmol) and diisopropylethylamine (0.141 mL, 0.809 mmol) in DMF was stirred at rt for 22 hr. The reaction mixture was partitioned between EtOAc (30 mL) and water (30 mL). The organic layer was washed with saturated potassium bisulfate solution (30 ml), saturated sodium bicarbonate solution (30 mL) and brine (30 mL). After drying (MgSO4) and filtration, the organic layer was concentrated to afford methyl 4-(methylcarbamoyl)-3-phenylisoxazole-5-carboxylate (38 mg, 0.146 mmol, 72.2% yield) as a tan solid. HPLC retention time=1.09 minutes (YMC Combi 4.6×30 mm S-5 ODS column) eluting with 10-90% aqueous methanol+0.1 TFA a 2 minute gradient. MS: (M+H)=261.15. 1H NMR (400 MHz, chloroform-d) d ppm 2.97 (d, J=4.77 Hz, 3H) 4.04 (s, 3 H) 7.19 (brs, 1H) 7.42-7.51 (m, 3H) 7.66-7.73 (m, 2H).
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