Sodium ethoxide → Ethyl 2-(4-((dimethylamino)methyl)phenyl)-7-fluoro-3-(1-methyl-1H-1,2,4-triazol-5-yl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate

HRID 1467787Notes

Reaction equation

[CH3:1][N:2]([CH2:4][C:5]1[CH:23]=[CH:22][C:8](/[CH:9]=[N:10]/[C:11]2[CH:19]=[C:18]([F:20])[CH:17]=[C:16]3[C:12]=2[CH2:13][O:14][C:15]3=[O:21])=[CH:7][CH:6]=1)[CH3:3].[CH3:24][N:25]1[C:29]([CH:30]=O)=[N:28][CH:27]=[N:26]1.[CH3:32][CH2:33][O-:34].[Na+]>C(OCC)(=O)CC>[CH3:1][N:2]([CH2:4][C:5]1[CH:23]=[CH:22][C:8]([CH:9]2[CH:30]([C:29]3[N:25]([CH3:24])[N:26]=[CH:27][N:28]=3)[C:33](=[O:34])[C:32]3[C:16]([C:15]([O:14][CH2:13][CH3:12])=[O:21])=[CH:17][C:18]([F:20])=[CH:19][C:11]=3[NH:10]2)=[CH:7][CH:6]=1)[CH3:3]

Participants

Conditions

Temperature: 48 °C

Procedure

To a solution of (E)-4-(4-((dimethylamino)methyl)benzylideneamino)-6-fluoroisobenzofuran-1(3H)-one (4.2 g, 13.5 mmol) and compound 1-methyl-1H-1,2,4-triazole-5-carbaldehyde (3.0 g, 27 mmol) in ethyl propionate (150 mL) was added rapidly NaOEt [sodium (870 mg, 37.8 mmol) in 70 mL ethanol] at 40° C., then the mixture was stirred at 48° C. for 3 hr. The resulting mixture was concentrated under reduced pressure and extracted with ethyl acetate (250 mL×3). The extract was evaporated to give a crude product, which was purified by column chromatography (silica gel, dichloromethane:methanol=50:1 to 10:1) to obtain the title compound (560 mg, yield 9%) (a mixture of cis and trans isomers). LC-MS (ESI) m/z: 452 (M+1)+.

Workup

concentrationThe resulting mixture was concentrated under reduced pressure
extractionextracted with ethyl acetate (250 mL×3)
customThe extract was evaporated
customto give a crude product, which
customwas purified by column chromatography (silica gel, dichloromethane:methanol=50:1 to 10:1)

Sources & evidence

ORD record: ord-91cc5f2b2eec4da5b1ae6af5d810d34b
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08999987B2

Reaction notes

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