Thioacetamide → 1,2-Diethyl 4-(aminothioxomethyl)tetrahydro-1,2-pyridazinedicarboxylate

HRID 75171Notes

Reaction equation

[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[N:5]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:4]1)#[N:2].C(N)(=[S:21])C>FC(F)(F)C(O)=O>[NH2:2][C:1](=[S:21])[CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[N:5]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:4]1

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of 1,2-diethyl 4-cyanotetrahydro-1,2-pyridazinedicarboxylate (i.e the product of Step E) (5.5 g, 0.024 mol) and thioacetamide (5.5 g, 0.073 mol) in trifluoroacetic acid (about 10 mL) was heated at 50° C. for 20 h. The reaction mixture was cooled, and then partitioned between water and diethyl ether (about 30 mL). The layers were separated and the aqueous layer was extracted with diethyl ether (2×). The combined organic extracts were washed with water (about 30 mL), dried magnesium sulfate, filtered and concentrated under reduce pressure to an orange oil. The oil was adsorbed onto Celite® (diatomaceous filter aid), and then purified by silica gel column chromatography (25% to 60% gradient of ethyl acetate in petroleum ether as eluant) to provide the title compound as a yellow solid (3.97 g).

Workup

temperatureThe reaction mixture was cooled
custompartitioned between water and diethyl ether (about 30 mL)
customThe layers were separated
extractionthe aqueous layer was extracted with diethyl ether (2×)
washThe combined organic extracts were washed with water (about 30 mL), dried magnesium sulfate
filtrationfiltered
concentrationconcentrated
custompurified by silica gel column chromatography (25% to 60% gradient of ethyl acetate in petroleum ether as eluant)

Sources & evidence

ORD record: ord-773be965097747278da923c4f415f9ce
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835427B2

Reaction notes

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