Triethylamine → Tert-butyl (6-carbamoyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate

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Reaction Steps

3-((tert-butoxycarbonyl)methyl)-[1,2,4]triazolo[4,3-b]pyridazine-6-carboxylic acid. In a 25 mL round bottom flask were dissolved 2-methyl-2-butene (21639 μl, 43278 μmol), potassium dihydrogen phosphate (2356 mg, 17311 μmol) and tert-butyl (6-formyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate (600 mg, 2164 μmol) in 5 mL of t-BuOH and 5 mL of water then was added at 0° C. sodium chlorite (783 mg, 8656 μmol) and the reaction mixture was warmed to rt. After 10 h the reaction mixture based on LC-MS was concentrated under reduced pressure and the crude acid was extract from the solid salts mixture with MeOH, filtered and the solvent was concentrated under reduced pressure. The crude 3-((tert-butoxycarbonyl)methyl)-[1,2,4]triazolo[4,3-b]pyridazine-6-carboxylic acid (635 mg, 100% yield) was used without further purification in the next step. MS m/z=294.2 [M+1]+. Calc'd for C12H15N5O4: 293.1 b) tert-butyl (6-carbamoyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate. In a 10 mL round bottom flask under N2 were dissolved 3-((tert-butoxycarbonyl)methyl)-[1,2,4]triazolo[4,3-b]pyridazine-6-carboxylic acid (250 mg, 852 μmol), HATU (389 mg, 1023 μmol), triethylamine (356 μl, 2557 μmol) in 1.5 mL of DMF then was treated with a (92 μl, 4262 μmol) and stirred at rt. After 2 h the reaction mixture based on LC-MS was concentrated under reduced pressure and then purified by MPLC (ISCO) with DCM:MeOH+NH4OH (1%) 100:0 to 90:10 to afforded tert-butyl (6-carbamoyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate (129 mg, 52% yield). MS m/z=293.2 [M+1]+. Calc'd for C12H16N6O3: 292.3.

Provenance & Evidence