Diisopropylethylamine → HCID 11964600, compound

HRID 1894137Notes

Reaction equation

CO[C:3](=[O:21])[C:4]1[CH:9]=[C:8]([C:10]2[N:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[C:7]([C:16]([F:19])([F:18])[F:17])=[CH:6][C:5]=1[NH2:20].ClC([O:25][C:26]1C=CC(Cl)=CC=1)=O.[CH3:33][S:34]([NH:37][NH2:38])(=[O:36])=[O:35].CCN(C(C)C)C(C)C>O1CCOCC1>[O:25]=[C:26]1[N:38]([NH:37][S:34]([CH3:33])(=[O:36])=[O:35])[C:3](=[O:21])[C:4]2[C:5](=[CH:6][C:7]([C:16]([F:17])([F:18])[F:19])=[C:8]([C:10]3[N:11]=[N:12][CH:13]=[CH:14][CH:15]=3)[CH:9]=2)[NH:20]1

Participants

Conditions

Temperature: 85 °C

Procedure

To a solution of 2-amino-5-pyridazin-3-yl-4-trifluoromethyl-benzoic acid methyl ester (79 mg, 0.266 mmol) in dioxane (4 mL) under argon was added 4-chlorophenyl chloroformate (44.6 μL, 0.319 mmol). The solution was stirred at 85° C. for 30 min and cooled to r.t. CH3SO2NHNH2 (58.5 mg, 0.531 mmol) and i-Pr2NEt (46.4 μL, 0.266 mmol) were added and the reaction mixture was heated back to 85° C. for 3 h. The mixture was concentrated in vacuo and the residue was purified by two consecutive flash chromatographies (silica gel, DCM→5% MeOH in DCM) then (silica gel, 7:3 EtOAc/hexanes). The product was suspended in a minimum amount of EtOAc, sonicated then taken into hexanes. The solid was collected by vacuum filtration to furnish the title compound (13 mg, 12%) as a white solid. API-ES: m/z 402.0 [M+H]+, rt 3.36 min, Method N—05—100: 5%→100% (6 min), 100% (1.5 min), 100%→5% (0.5 min)

Workup

temperaturecooled to r.t
temperaturethe reaction mixture was heated back to 85° C. for 3 h
concentrationThe mixture was concentrated in vacuo
customthe residue was purified by two consecutive flash chromatographies (silica gel, DCM→5% MeOH in DCM)
customsonicated
filtrationThe solid was collected by vacuum filtration

Sources & evidence

ORD record: ord-289e7575c7eb4689913c5307ea2b64f3
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08513268B2

Reaction notes

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