Dimethyl Sulfoxide → 1-(6((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)-1H-pyrrole-3-carboxamide

HRID 869189Notes

Reaction equation

[C:1]([C:3]1[CH:7]=[CH:6][N:5]([C:8]2[N:13]=[N:12][C:11]([N:14]([CH2:22][C:23]3([C:27]4[C:32]([F:33])=[CH:31][CH:30]=[CH:29][N:28]=4)[CH2:26][CH2:25][CH2:24]3)C(=O)OC(C)(C)C)=[CH:10][CH:9]=2)[CH:4]=1)#[N:2].C(=O)([O-])[O-:35].[K+].[K+].CS(C)=O.OO>C(OCC)(=O)C>[F:33][C:32]1[C:27]([C:23]2([CH2:22][NH:14][C:11]3[N:12]=[N:13][C:8]([N:5]4[CH:6]=[CH:7][C:3]([C:1]([NH2:2])=[O:35])=[CH:4]4)=[CH:9][CH:10]=3)[CH2:26][CH2:25][CH2:24]2)=[N:28][CH:29]=[CH:30][CH:31]=1

Participants

Conditions

Temperature: 0 °C

Procedure

t-butyl 6-(3-cyano-1H-pyrrol-1-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (120 mg, 267 μmol), potassium carbonate (147 mg, 1.1 mmol), and DMSO (3 mL) were combined in a vial and cooled to 0° C. Hydrogen peroxide (700 uL) was added dropwise, and the reaction was warmed to rt and stirred for 1 h. The reaction was then poured into ethyl acetate (50 mL), washed with water (3×20 mL), and the organic layer was separated, dried over Na2SO4, filtered, and concentrated. The crude solid was dissolved in 50% TFA/CH2Cl2 (2 mL) and stirred for 30 min. The reaction was then concentrated and purified using reverse phase chromatography to give 29 mg of 1-(6((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)-1H-pyrrole-3-carboxamide as a tan solid (M+H=367.1).

Workup

temperaturethe reaction was warmed to rt
washwashed with water (3×20 mL)
customthe organic layer was separated
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
dissolutionThe crude solid was dissolved in 50% TFA/CH2Cl2 (2 mL)
stirringstirred for 30 min
concentrationThe reaction was then concentrated
custompurified

Sources & evidence

ORD record: ord-8eebf5c229d24111a18b972867ef868f
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08969346B2

Reaction notes

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