3-Amino-5-methylisoxazole → HCID 58236596, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 370 (0.14 g, 0.25 mmol) and DIPEA (0.11 mL, 0.080 g, 0.61 mmol) in tetrahydrofuran (50 mL) at 0° C. was added triphosgene (0.030 g, 0.10 mmol) and the resulting solution was stirred for 0.5 h at 0° C. 3-Amino-5-methylisoxazole (0.074 g, 0.76 mmol) was added and the mixture was warmed to room temperature and stirred for 3 h, then quenched with 1 mL of water and concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water; the organic phase was collected, washed with brine, dried over MgSO4, filtered and concentrated. The product was purified by silica gel chromatography (10% MeOH in EtOAc), followed by Gilson reverse phase HPLC (35-65% acetonitrile/H2O, Aquasil C18, 30 min) and lyophilized. The residue (containing some formic acid from the HPLC) was partitioned between dichloromethane and 1M NaOH. The organic phase was dried (MgSO4), filtered and concentrated to give 371 (65 mg, 38% yield) as a 2:1 mixture of rotamers by 1H NMR. 1H NMR (DMSO-d6) δ (ppm) 1H: 9.64 (s, 1H); 9.19 (s, 1H); 8.50-8.48 (m, 1H); 8.04 (s, 0.4H); 8.01 (s, 0.6H); 7.89 (d, J=8.2, 0.4H); 7.82 (d, J=8.2, 0.6H); 7.72 (dd, J=12.9, 2.5, 1H); 7.45 (t, J=9.2, 1H); 7.33 (d, J=8.4, 2H); 7.27-7.24 (m, 1H); 6.61-6.59 (m, 1H); 6.54 (d, J=0.8, 1H); 4.68 (s, 0.4H); 4.59 (s, 0.6H); 3.52-3.38 (m, 12H); 3.21 (s, 1.8H); 3.20 (s, 1.2H); 2.35 (d, J=0.4, 3H); 2.12 (s, 1.8H); 2.00 (1.2H). LRMS (M+H): 678.8

Provenance & Evidence