(1R)-2,2-dimethylcyclopentan-1-amine

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of Preparation 5 (41.8 mg, 0.152 mmol) and (±)-(1S,2S)-2-amino-1-methylcyclohexanol hydrobromide (32 mg, 0.152 mmol) in DMF (0.4 mL) was added DIPEA (0.08 mL, 0.46 mmol) and the mixture was heated to 90° C. for 18 h. The reaction was cooled to rt and added water (3 mL) then stirred rapidly for 3 h and filtered. The solids were purified on silica gel (100% heptane to 50% ethyl acetate/heptane to 100% ethyl acetate) to afford the title compound (31.6 mg, 57% yield). LCMS 369.05 (M+2)+. The reaction was cooled to rt filtered The solids were purified on silica gel (100% heptane to 50% ethyl acetate/heptane to 100% ethyl acetate)

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 6-bromo-4-chloropyrrolo[1,2-b]pyridazine-3-carboxamide (Preparation 5, 300 mg, 1.093 mmol) and (R)-2,2-dimethylcyclopentanamine (from Step 3 of Intermediate 5, 164 mg, 1.093 mmol) in DMF (4 mL) was added DIPEA (0.573 mL, 3.28 mmol). The mixture was heated at 120° C. for 60 min in a microwave reactor. Water (4 volumes) was added and the resulting suspension was stirred for 1 h. The solids were filtered, rinsed with water (2×), and then dried to afford the title compound (324 mg, 84% yield) as a pale yellow solid. HPLC (conditions 0): retention time=4.07 min; LCMS: 351.01 (M+), 353.00 (M+2); 1H NMR (methanol-d4, 400 MHz) δ 8.14 (s, 1H), 7.62 (d, J=1.8 Hz, 1H), 7.02 (d, J=1.8 Hz, 1H), 4.15 (t, J=7.3 Hz, 1H), 2.32 (m, 1H), 1.61-1.86 (m, 5H), 1.13 (s, 3H), 1.10 (s, 3H). The solids were filtered rinsed with water (2×) dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Prepared by reacting (R)-2,2-dimethylcyclopentylamine with ethyl 3-carbamoyl-4-chloropyrrolo[1,2-b]pyridazine-6-carboxylate (Preparation 4) according to the procedure described in Step 5 of Intermediate 4. HPLC (condition B): retention time=3.67 min. LCMS (condition E): m/z 345+ve. 1H NMR (400 MHz, MeOD) δ ppm 10.86 (1 H, br. s.), 8.20 (1 H, s), 8.01 (1 H, d, J=1.76 Hz), 7.38 (1 H, d, J=1.54 Hz), 4.27-4.43 (2 H, m), 4.13-4.29 (1 H, m), 2.29-2.46 (1 H, m), 1.58-1.92 (5 H, m), 1.38 (3 H, t, J=7.15 Hz), 1.13 (3 H, s), 1.10 (3 H, s). Prepared