4-Fluorobenzoic Acid → 2-[3-(4-Fluoro-benzoylamino)-phenyl]-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid

HRID 2045189Notes

Reaction equation

[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[CH:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:23][C:24]1[CH:25]=[C:26]([CH:30]2[C:39]([CH3:41])([CH3:40])[CH2:38][C:37]3[C:32](=[CH:33][CH:34]=[C:35]([C:42]([OH:44])=[O:43])[CH:36]=3)[NH:31]2)[CH:27]=[CH:28][CH:29]=1>CN(C)C=O>[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:23][C:24]2[CH:25]=[C:26]([CH:30]3[C:39]([CH3:40])([CH3:41])[CH2:38][C:37]4[C:32](=[CH:33][CH:34]=[C:35]([C:42]([OH:44])=[O:43])[CH:36]=4)[NH:31]3)[CH:27]=[CH:28][CH:29]=2)=[O:7])=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A solution of 4-fluoro-benzoic acid (119 mg, 0.85 mmol) and 1,1′-carbonyldiimidazole (179 mg, 1.1 mmol) in N,N-dimethylformamide (1.5 mL) was stirred at 70° C. for 1 h. Then a solution of 2-(3-amino-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (200 mg, 0.68 mmol) in N,N-dimethylformamide (1.5 mL) was added and the mixture was allowed to stir at 50° C. for 3 h. Purification by Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% formic acid in water) afforded 2-[3-(4-fluoro-benzoylamino)-phenyl]-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (44 mg, 15%) as a white solid: LC/MS m/e calcd for C25H23FN2O3 (M+H)+: 419.47, observed: 419.1.

Workup

customPurification by Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% formic acid in water)

Sources & evidence

ORD record: ord-d36b13fd608e4d5aae4f9ebb2538f112
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08586747B2

Reaction notes

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