[N:1]1[C:10]2[C:5](=[CH:6][C:7]([CH2:11][C:12]3[N:16]4[N:17]=[C:18]([C:21]#[N:22])[CH:19]=[CH:20][C:15]4=[N:14][CH:13]=3)=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[OH-:23].[Na+].Cl.[C:26](Cl)(=O)[C:27](Cl)=O.C(N)C>CO>[CH2:26]([NH:22][C:21]([C:18]1[CH:19]=[CH:20][C:15]2[N:16]([C:12]([CH2:11][C:7]3[CH:6]=[C:5]4[C:10](=[CH:9][CH:8]=3)[N:1]=[CH:2][CH:3]=[CH:4]4)=[CH:13][N:14]=2)[N:17]=1)=[O:23])[CH3:27]
3-Quinolin-6-ylmethyl-imidazo[1,2-b]pyridazine-6-carbonitrile (Example 208; 43 mg, 0.15 mmol) in a 1 M aqueous solution of NaOH (1.8 mL, 1.8 mmol) was heated under microwave irradiation at 200° C. for 30 min. The RM was quenched with a 2 M aqueous solution of HCl (0.9 mL, 1.8 mmol) and diluted with MeOH and filtered over Celite. The filtrate is evaporated and dry under vacuo. The residue was suspended in DCM (3 mL) and cooled at 0° C. Were added DMF (0.01 mL) and, slowly, oxalyl chloride (0.055 mL, 0.65 mmol). The RM was allowed to reach rt and stirred at this temperature for 45 min. The RM was dropped in a 2 M solution of ethylamine in MeOH (6 mL). The RM was stirred at rt for 5 min before being evaporated to dryness and the residue quenched with aqueous saturated NaHCO3 and diluted with EtOAc. The aqueous layer was extracted with EtOAc and the combined organic layers were washed with brine and dried over Na2SO4, filtered and evaporated. The residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA) to yield the title compound as light yellow solid (tR 1.96 min (conditions 8), MH+=332).
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