[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[C:11]1[S:20][C:14]2[C:15](=O)[NH:16][N:17]=[CH:18][C:13]=2[CH:12]=1.P(Cl)(Cl)([Cl:23])=O.[CH:26]1([NH2:29])[CH2:28][CH2:27]1>OS([O-])(=O)=O.[K+]>[Cl:23][C:15]1[N:16]=[N:17][CH:18]=[C:13]2[CH:12]=[C:11]([C:3]3[CH:4]=[C:5]([CH:9]=[CH:10][C:2]=3[CH3:1])[C:6]([NH:29][CH:26]3[CH2:28][CH2:27]3)=[O:8])[S:20][C:14]=12A mixture of 4-methyl-3-(7-oxo-6,7-dihydrothieno[2,3-d]pyridazin-2-yl)benzoic acid (1.01 g, 3.53 mmol) and phosphorus oxychloride (30.0 ml, 322 mmol) was heated to 105° C. for 4 hrs. After cooling to RT, the volatiles were removed in vacuo. The residue was re-dissolved in DCM (50 ml) and treated with TEA (1.49 ml, 10.6 mmol) and dropwise with cyclopropylamine (0.746 ml, 10.6 mmol). The mixture was diluted with 1 M KHSO4 and extracted with CH2Cl2 (3×). The combined organics were dried over Na2SO4, filtered and concentrated over SiO2. Column chromatography (MeOH/CH2Cl2=0→2%) afforded the desired product. Yield: 0.92 g. MS (ESI, pos. ion) m/z: 344 (M+1).
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