[Br:1][C:2]1[CH:3]=[C:4]2[C:9](Cl)=[C:8]([C:11]([NH2:13])=[O:12])[CH:7]=[N:6][N:5]2[CH:14]=1.Cl.[NH2:16][C@H:17]([CH3:23])[C:18]([CH3:22])([CH3:21])[C:19]#[N:20].CCN(C(C)C)C(C)C>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9]([NH:16][C@@H:17]([C:18]([C:19]#[N:20])([CH3:22])[CH3:21])[CH3:23])=[C:8]([C:11]([NH2:13])=[O:12])[CH:7]=[N:6][N:5]2[CH:14]=1To a suspension of 6-bromo-4-chloropyrrolo[1,2-b]pyridazine-3-carboxamide (250 mg, 0.911 mmol) and (R)-3-amino-2,2-dimethylbutanenitrile hydrochloride (165 mg, 0.408 mmol) in DMF (10 mL) taken in a pressure tube (25 mL) was added DIPEA (0.477 mL, 2.73 mmol) at rt. The resulting reaction mixture was heated 100° C. and stirred for overnight. Reaction was monitored by LCMS. Reaction mass was quenched with water (50 mL) and extracted with ethyl acetate (3×30 mL). The combined organic layer was dried and concentrated under reduced pressure to get crude as brown colored oil. The crude was purified by combiflash using 24 g silicycle column eluted with 50% EA in hexane. The fractions were concentrated under reduced pressure to get (R)-6-bromo-4-((3-cyano-3-methylbutan-2-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (165 mg, 0.408 mmol, 44.7% yield) as pale brown solid. 1HNMR (400 MHz, DMSO-d6) δ ppm: 11.16-11.13 (d, J=9.6 Hz, 1H), 8.32 (s, 1H), 7.96-7.93 (d, J=13.2 Hz, 2H), 7.92 (bs, 2H), 7.22-7.21 (d, J=1.6 Hz, 2H), 4.43-4.39 (q, J=6.4, 3.6 and 6.4 Hz, 1H), 1.43-1.35 (m, 9H). HPLC purity: Column: Sunfire C18 (4.6×150 mm, 3.5μ, Buffer: 0.05% TFA in H2O pH 2.5, Solvent A: Buffer: CH3CN (95:5). Solvent B: Buffer: CH3CN (5:95). Time: 0-10, 12-100, 15-100 min, Flow: 1.0 mL/min Retention Time: 9.68: Purity: 91.94%. LCMS Purity: Column: Purospher@star RP-18 (4×55) mm, 3 μm. Buffer: 20 mM NH4OAc in water Mobile Phase A: Buffer: CH3CN (90:10). Solvent B: Buffer: CH3CN (10:90).Flow: 2.5 mL/min, Time: 0-0, 2-100, 2.5-100, 3.0-0 min. Retention Time: 1.688 min. Purity: 91.5% (m/z=348.2 M-2).
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