Diisopropylethylamine → 4-((1R,3 S)-3-amino-2,2,3-trimethylcyclopentylamino)-6-bromopyrrolo[1,2-b]-pyridazine-3-carboxamide

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Reaction Conditions

Reaction Steps

A solution of 6-bromo-4-chloropyrrolo[1,2-b]pyridazine-3-carboxamide (Preparation 5, 638 mg, 2.325 mmol) and (1S,3R)-1,2,2-trimethylcyclopentane-1,3-diamine (prepared as described in Intermediate 10, 430 mg, 3.02 mmol) in DMF (3.5 mL) was added DIPEA (1.218 mL, 6.98 mmol). The reaction vessel was purged with N2, sealed and heated to at 95° C. for 90 min. The reaction was cooled and partitioned between ethyl acetate (35 mL) and water (20 mL). The layers were separated and the aqueous layer further extracted with ethyl acetate (2×). The combined organic extracts were dried (Na2SO4), filtered and concentrated. The crude extracts were combined with two previous reactions and concentrated onto SiO2 and eluted onto a silica gel column with 100% ethyl acetate. After the non-polar impurities had eluted, the solvent was changed to 5% MeOH/CH2Cl2 then 10% then 15% MeOH/CH2Cl2 to afford the title compound (2.113 grams, 67% yield). HPLC (condition 0): retention time=2.61 min; LCMS: 382.08 (M+2); 1H NMR (methanol-d4, 400 MHz) δ 8.14 (s, 1H), 7.63 (d, J=1.8 Hz, 1H), 6.93 (d, J=1.8 Hz, 1H), 4.41 (t, J=8.4 Hz, 1H), 2.34 (m, 1H), 1.85 (m, 2H), 1.70 (m, 1H), 1.22 (s, 3H), 1.08 (s, 3H), 0.96 (s, 3H).

Provenance & Evidence