Methanol → Ethyl 6-iodo-[1,2,4]triazolo[4,3-b]pyridazine-3-carboxylate

Temperature

40 °C

In a 1 L round-bottomed flask was added 3-hydrazinyl-6-iodopyridazine (60.6 g, 257 mmol, prepared using General Procedure D from 3-chloro-6-iodopyridazine [Example #9 Step A] with hydrazine hydrate) and MeOH (600 mL) to give a tan suspension. A solution of glyoxylic acid ethyl ester (50 wt % in toluene, 54.9 mL, 270 mmol, Fluka) was added. The mixture was heated at about 40° C. for about 2 h. The reaction mixture was cooled to ambient temperature and the solvent was removed in vacuo. The residue was dissolved in DCM (600 mL) and iodobenzene diacetate (99.0 g, 308 mmol) was added and the mixture was stirred overnight. The reaction mixture was diluted with additional DCM (600 mL) and extracted with water (600 mL). The organic layer was dried over MgSO4 and concentrated in vacuo. The solid was triturated with EtOAc (500 mL) and then collected by filtration. The solid was washed with additional EtOAc (250 mL) and then dried in vacuo to give title compound (53.9 g, 65%). LC/MS (Table 1, Method g) Rt=1.18 min; MS m/z: 319.0 (M+H)+. 1H NMR (DMSO-d6) δ 8.29 (m, 1H), 7.84 (m, 1H), 4.48 (m, 2H), 1.39 (t, 3H).

1. customto give a tan suspension
2. temperatureThe reaction mixture was cooled to ambient temperature
3. customthe solvent was removed in vacuo
4. dissolutionThe residue was dissolved in DCM (600 mL)
5. extractionextracted with water (600 mL)
6. dry with materialThe organic layer was dried over MgSO4
7. concentrationconcentrated in vacuo
8. customThe solid was triturated with EtOAc (500 mL)
9. filtrationcollected by filtration
10. washThe solid was washed with additional EtOAc (250 mL)
11. customdried in vacuo

ORD record

ord-e48659f8146349e6bb38418c72318ba8

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08188083B2