N,N-Dimethylglycine → 1-(4-Fluorophenyl)-6-((6-methylpyridin-3-yl)oxy)-4-oxo-1,4-dihydroquinoline-3-carboxamide

HRID 1048891Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)[CH:7]=[C:6]([C:19]([NH2:21])=[O:20])[C:5]2=[O:22].[OH:23][C:24]1[CH:25]=[CH:26][C:27]([CH3:30])=[N:28][CH:29]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)CC(O)=O>CN(C=O)C.[Cu]I>[F:18][C:15]1[CH:16]=[CH:17][C:12]([N:8]2[C:9]3[C:4](=[CH:3][C:2]([O:23][C:24]4[CH:29]=[N:28][C:27]([CH3:30])=[CH:26][CH:25]=4)=[CH:11][CH:10]=3)[C:5](=[O:22])[C:6]([C:19]([NH2:21])=[O:20])=[CH:7]2)=[CH:13][CH:14]=1

Participants

Conditions

Temperature: 150 °C

Procedure

Compound E (15 mg, 0.042 mmol, 1.0 eq), 5-hydroxy-2-methylpyridine (9.1 mg, 0.083 mmol, 2.0 eq), cesium carbonate (27 mg, 0.083 mmol, 2.0 eq), copper(I) iodide (0.79 mg, 0.0042 mmol, 0.10 eq) and N,N-dimethylglycine (1.3 mg, 0.013 mmol, 0.30 eq) were dissolved in DMF in a microwave vial and heated in a microwave reactor at 150° C. for 15 minutes. The reaction was filtered over Celite® and washed with 5% methanol in DCM. The organics were concentrated and purified using reverse phase chromatography to afford 9.1 mg (56%) of title compound as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 9.12 (d, J=4.3 Hz, 1H), 8.54 (s, 1H), 8.33 (d, J=2.8 Hz, 1H), 7.77-7.73 (m, 2H), 7.68 (d, J=3.0 Hz, 1H), 7.59 (d, J=4.3 Hz, 1H), 7.56-7.47 (m, 4H), 7.34 (d, J=8.5 Hz, 1H), 7.12 (d, J=9.2 Hz, 1H), 2.49 (s, 3H); ES-MS [M+1]+: 390.4.

Workup

filtrationThe reaction was filtered over Celite®
washwashed with 5% methanol in DCM
concentrationThe organics were concentrated
custompurified

Sources & evidence

ORD record: ord-44316890c31f49e4b2409b54b13a59a0
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382208B1

Reaction notes

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