Tetrahydrofuran → N-cyclopropyl-N'-{2-[(3-fluoro-4-methylphenyl)amino]pyridin-3-yl}ethanediamide

HRID 2272692Notes

Reaction equation

CC(C)([O-])C.[K+].[F:7][C:8]1[CH:9]=[C:10]([NH:15][C:16]2[C:21]([NH2:22])=[CH:20][CH:19]=[CH:18][N:17]=2)[CH:11]=[CH:12][C:13]=1[CH3:14].C([O:25][C:26](=O)[C:27]([NH:29][CH:30]1[CH2:32][CH2:31]1)=[O:28])C.O1CCCC1>CN1CCCC1=O.[Cl-].[NH4+].C(OCC)(=O)C>[CH:30]1([NH:29][C:27](=[O:28])[C:26]([NH:22][C:21]2[C:16]([NH:15][C:10]3[CH:11]=[CH:12][C:13]([CH3:14])=[C:8]([F:7])[CH:9]=3)=[N:17][CH:18]=[CH:19][CH:20]=2)=[O:25])[CH2:32][CH2:31]1

Participants

Conditions

Temperature: 120 °C

Procedure

Potassium tert-butoxide (4.54 g, 40.5 mmol) was added to a solution of N2-(3-fluoro-4-methylphenyl)pyridine-2,3-diamine (C2) (from the previous step, 5.87 g, 24.4 mmol) and ethyl(cyclopropylamino)(oxo)acetate (P1) (6.36 g, 40.5 mmol) in 1-methylpyrrolidin-2-one (27 mL). The reaction mixture was heated at 120° C. for 10 minutes, cooled to room temperature and diluted with aqueous ammonium chloride solution. Tetrahydrofuran was added to assist solubilization, followed by ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated in vacuo to provide the crude product (13.0 g). A portion of this material was used directly in the following step. LCMS m/z 329.0 [M+H]+.

Workup

temperaturecooled to room temperature
washThe organic layer was washed with saturated aqueous sodium chloride solution
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-65777bdbd1f54d8cbe1175bc428b2683
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09120788B2

Reaction notes

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