Tetrahydrofuran → 4-(Imidazo[1,2-b]pyridazin-3-yl)-5-methylthiophene-2-carboxylic acid

HRID 2046403Notes

Reaction equation

[N:1]1[CH:2]=[C:3]([C:10]2[CH:11]=[C:12]([C:16]([O:18]C)=[O:17])[S:13][C:14]=2[CH3:15])[N:4]2[C:9]=1[CH:8]=[CH:7][CH:6]=[N:5]2.C1COCC1.[OH-].[K+]>CO>[N:1]1[CH:2]=[C:3]([C:10]2[CH:11]=[C:12]([C:16]([OH:18])=[O:17])[S:13][C:14]=2[CH3:15])[N:4]2[C:9]=1[CH:8]=[CH:7][CH:6]=[N:5]2

Participants

Conditions

Temperature: 60 °C

Procedure

Methyl 4-(imidazo[1,2-b]pyridazin-3-yl)-5-methylthiophene-2-carboxylate (0.54 g, 1.98 mmol) was dissolved in methanol (9.88 mL) and THF (9.88 mL) and a solution of KOH in methanol was added (1 M, 5.93 mL, 5.93 mmol). The reaction mixture was left to stir overnight at 60° C. The reaction mixture was then cooled to room temperature, concentrated, and acidified with aqueous 1N HCl. The aqueous layer was extracted three times with ethyl acetate, then extracted one time with a 3:1 CHCl3:isopropanol mixture. The combined organics were dried with magnesium sulfate, filtered, and concentrated to afford the title compound. 1H NMR (500 MHz, CD3SOCD3) δ 8.77 (d, 1H); 8.34 (d, 1H); 8.25 (s, 1H); 8.11 (s, 1H); 7.51 (dd, 1H); 2.56 (s, 3H). LRMS (APCI) calc'd for (C12H9N3O2S) [M+H]+, 260.0. found 260.0.

Workup

waitThe reaction mixture was left
temperatureThe reaction mixture was then cooled to room temperature
concentrationconcentrated
extractionThe aqueous layer was extracted three times with ethyl acetate
extractionextracted one time with a 3:1 CHCl3
dry with materialThe combined organics were dried with magnesium sulfate
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-a4700d4c094d4b6fbeae3b65e75c56c4
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08592425B2

Reaction notes

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