Dimethylformamide → 7-Bromo-1-cyclopropyl-6-fluoro-2-methylsulfanyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester
Reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6](=[O:25])[C:7]([CH2:15][C:16]1[CH:21]=[C:20]([F:22])[C:19]([Br:23])=[CH:18][C:17]=1F)=[C:8]([NH:11][CH:12]1[CH2:14][CH2:13]1)[S:9][CH3:10])[CH3:4].CN(C=[O:30])C>[NH4+].[Cl-]>[CH2:3]([O:5][C:6]([C:7]1[C:15](=[O:30])[C:16]2[C:17](=[CH:18][C:19]([Br:23])=[C:20]([F:22])[CH:21]=2)[N:11]([CH:12]2[CH2:14][CH2:13]2)[C:8]=1[S:9][CH3:10])=[O:25])[CH3:4]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 75 °C
Procedure
NaH (345 mg, 60% in mineral oil, 8.6 mmole, 1.05 equiv.) is added to a stirred solution of 2-(4-bromo-2,5-difluoro-benzyl)-3-cyclopropylamino-3-methylsulfanyl-acrylic acid ethyl ester (4, 3.46 g, 8.2 mmole) in DMF (anhydrous, 100 ml). The reaction mixture is stirred at 75° C. for 18 hours (TLC is used to indicate reaction completion). The reaction mixture is cooled, diluted with NH4Cl solution, and extracted with EtOAc. The organics are washed with brine (4×30 ml), dried over Na2SO4, and concentrated in vacuo to give 5 as a light yellow solid. This intermediate is used without further purification 1H NMR (CDCl3) indicated >98% purity). 1HNMR (CDCl3) δ: 8.09 (d, 1H), 7.90 (d, 1H), 4.35 (q, 2H), 3.22 (m, 1H), 2.49 (s, 3H), 1.3-1.5 (m, 7H).
Workup
- custom(TLC is used to indicate reaction completion)
- temperatureThe reaction mixture is cooled
- extractionextracted with EtOAc
- washThe organics are washed with brine (4×30 ml)
- dry with materialdried over Na2SO4
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-e8c646035780459bb65a68a0b6c02ef4
- Source dataset
- uspto-grants-2012_02
- Patent number
- US08114888B2
Reaction notes
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