Formic Acid → 3-(2-Fluorophenyl)-7-(3-hydroxycyclobutyl)-1,2,4-triazolo[4,3-b]pyridazin-6-one

HRID 1369447Notes

Reaction equation

C(O)=O.C([O:11][CH:12]1[CH2:15][CH:14]([C:16]2[C:21](=[O:22])[NH:20][N:19]3[C:23]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=4[F:32])=[N:24][N:25]=[C:18]3[CH:17]=2)[CH2:13]1)C1C=CC=CC=1.C([O-])=O.[NH4+]>CO>[F:32][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=1[C:23]1[N:19]2[NH:20][C:21](=[O:22])[C:16]([CH:14]3[CH2:13][CH:12]([OH:11])[CH2:15]3)=[CH:17][C:18]2=[N:25][N:24]=1

Participants

Conditions

Temperature: 60 °C

Procedure

Formic acid (8 ml) was added to a solution of 7-(3-benzyloxycyclobutyl)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazin-6-one (0.64 g, 1.64 mmol) and ammonium formate (1.034 g, 16.4 mmol) in methanol (40 ml). The solution was flushed with nitrogen and 10% palladium on carbon (0.3 g) was added. The resulting solution was stirred under an atmosphere of nitrogen for 2 hours at 60° C. The reaction was cooled, filtered, and concentrated under vacuum. The residue was purified by chromatography on silica using 0-10% methanol/dichloromethane as eluent to give the required product as a white solid. Data for the title compound: 1H NMR (360 MHz, DMSO), cis and traits isomers present in 5.5:1 ratio, δ1.89-1.98 (1.7H, m), 2.21-2.29 (0.3H, m), 2.40-2.48 (0.3H, m), 2.55-2.65 (1.7H, m), 2.88-3.00 (1H, m), 4.06-4.14 (0.85H, m), 4.20-4.30 (0.15H, m), 7.38-7.47 (2H, m), 7.60-7.65 (1H, m), 7.80-7.85 (1H, m), 7.97 (0.85H, s), 8.12 (0.15H, s); MS (ES+) m/e 301 [MH]+.

Workup

customThe solution was flushed with nitrogen and 10% palladium on carbon (0.3 g)
additionwas added
temperatureThe reaction was cooled
filtrationfiltered
concentrationconcentrated under vacuum
customThe residue was purified by chromatography on silica using 0-10% methanol/dichloromethane as eluent

Sources & evidence

ORD record: ord-c3808bd4e3524dcb9448d542bae92be4
Source dataset: uspto-grants-2003_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06579875B1

Reaction notes

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