Ammonium Chloride → HCID 68358605, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of (1S,3R)-3-(3-carbamoyl-6-phenylpyrrolo[1,2-b]pyridazin-4-ylamino)-1,2,2-trimethylcyclopentanecarboxylic acid (30 mg, 0.074 mmol) in DMF (492 μl) were added Hunig's base (97 μl, 0.554 mmol) and HATU (42.1 mg, 0.111 mmol). After 15 minutes, ammonium chloride (19.74 mg, 0.369 mmol) was added. The reaction was heated at 75° C. for 24 hrs. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. The solution was washed successively with water, (sat.) ammonium chloride and (sat.) sodium chloride. The ethyl acetate extract was dried with sodium sulfate, filtered, and concentrated under reduced pressure, yielding a yellow oil. The crude product was chromatographed using reverse-phase HPLC (Column: LUNA 5u C18 21×100). The collected fractions were combined and concentrated under reduced pressure. The product was taken up in ethyl acetate and neutralized with (sat.) sodium carbonate. The ethyl acetate extract was dried with sodium sulfate, filtered, and concentrated under reduced pressure to afford the title compound (12.7 mg, 0.030 mmol, 40.3% yield) as a white solid. LC/MS found [M+H]+=406.2. 1H NMR (400 MHz, MeOD) δ ppm 8.13-8.17 (1 H, m), 7.92-7.96 (1 H, m), 7.64-7.70 (2 H, m), 7.35-7.44 (2 H, m), 7.23-7.30 (1 H, m), 7.15-7.20 (1 H, m), 4.68-4.77 (1 H, m), 2.54-2.67 (1 H, m), 2.41-2.54 (1 H, m), 1.70-1.80 (1 H, m), 1.60-1.69 (1 H, m), 1.35-1.42 (3 H, m), 1.13-1.19 (3 H, m), 1.06-1.13 (3H, m). HPLC Retention Time=3.058 (HPLC conditions: column. Phenominex Synergy, 4.6×50 mm, Mobile phase A: 90:10 water/methanol with 0.2% H3PO4; Mobile Phase B: 90:10 methanol/water with 0.2% H3PO4; Wavelength: 220 nm; Gradient: 0-100% B over 4 minutes, then a 1-minute hold at 100% B; Flow: 4 mL/min.)

Provenance & Evidence