Methanol → Methyl 6-chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazine-8-carboxylate

HRID 521561Notes

Reaction equation

S(Cl)(Cl)=O.[Cl:5][C:6]1[CH:7]=[C:8]([C:16]([OH:18])=[O:17])[C:9]2[N:10]([C:12]([CH3:15])=[N:13][N:14]=2)[N:11]=1.[CH3:19]O>>[Cl:5][C:6]1[CH:7]=[C:8]([C:16]([O:18][CH3:19])=[O:17])[C:9]2[N:10]([C:12]([CH3:15])=[N:13][N:14]=2)[N:11]=1

Participants

Reactant 3

HCID 887Methanol

HCID 24386Thionyl Chloride

HCID 729431896-Chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazine-8-carboxylic acid

Product 1

HCID 89287517Methyl 6-chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazine-8-carboxylateYield 72%

Conditions

Temperature: 80 °C

Procedure

Thionyl chloride (2.0 mL) was added dropwise to a solution of 6-chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazine-8-carboxylic acid (4.0 g, 18.5 mmol) in MeOH (100 mL) under cooling in an ice bath. The resulting mixture was stirred at 80° C. for more than 16 h. The reaction mixture was then cooled to room temperature and concentrated, and the crude product was purified by flash chromatography (silica gel, 1% to 10% MeOH in CH2Cl2) to give the methyl 6-chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazine-8-carboxylate as a yellow solid (3.0 g, 72% yield). 1H NMR (300 MHz, CD3OD): δ 7.92 (s, 1H), 4.07 (s, 3H), 2.79 (s, 3H). LRMS [M+H]+: 226 m/z.

Workup

temperatureunder cooling in an ice bath
temperatureThe reaction mixture was then cooled to room temperature
concentrationconcentrated
customthe crude product was purified by flash chromatography (silica gel, 1% to 10% MeOH in CH2Cl2)

Sources & evidence

ORD record: ord-1a36c7756b9c4532a72010a7fda55a47
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328117B2

Reaction notes

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