3-Fluoroaniline → HCID 178461355, compound

HRID 1826908Notes

Reaction equation

HRID 1826908 reaction equation
Cl.FC1C=CC=C2C=1C=C(C(O)=O)C=N2.Cl.[F:17][C:18]1[CH:27]=[C:26]2[C:21]([CH:22]=[C:23]([C:28]([OH:30])=O)[CH:24]=[N:25]2)=[CH:20][CH:19]=1.FC1C=C(C=CC=1)N.C(Cl)(=O)C(Cl)=O.Cl.[CH3:46][C@H:47]1[CH2:52][CH2:51][C@H:50]([NH2:53])[CH2:49][CH2:48]1>ClCCl.CN(C)C=O.C(OCC)(=O)C.CCCCCC>[CH3:46][C@H:47]1[CH2:52][CH2:51][C@H:50]([NH:53][C:28]([C:23]2[CH:24]=[N:25][C:26]3[C:21]([CH:22]=2)=[CH:20][CH:19]=[C:18]([F:17])[CH:27]=3)=[O:30])[CH2:49][CH2:48]1

Participants

10

Reactant 5

HCID 97423-FluoroanilineHCID 65578Oxalyl chlorideHCID 69658464HCID 69658464, compoundHCID 69659148HCID 69659148, compoundHCID 178461307HCID 178461307, compound

Product 1

HCID 178461355HCID 178461355, compound

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

The methods of Erickson (J. Med. Chem., 1979, 22, 7, 816–823) were used to prepare a mixture of 5-fluoroquinoline-3-carboxylic acid hydrochloride and 7-fluoroquinoline-3-carboxylic acid hydrochloride from m-fluoroaniline. A mixture of these two acids (500 mg, 2.2 mmole) in dichloromethane (25 mL) was treated with a solution of oxalyl chloride in dichloromethane (1.2 mL of 2 M, 2.4 mmol) followed by dimethylformamide (5 drops). The reaction was stirred overnight, filtered (Gelman Acrodisc CR PTFE 0.45 micron) and concentrated to a solid. The solid was dissolved in dichloromethane (25 mL) and then treated with trans-4-methylcyclohexylamine hydrochloride (330 mg, 2.2 mmol) followed by 4-N,N′-dimethylaminopyridine (1.22 g, 10 mmol). The reaction was stirred 1 hour at ambient temperature. Chromatography of the crude reaction mixture through a Biotage silica cartridge (8×4 cm i.d.) using a gradient of hexane to 30% ethyl acetate (in hexane) afforded three fractions. Recrystallization of fraction A from hot heptane afforded 30 mg of N-(trans-4-methylcyclohexyl)-7-fluoroquinoline-3-carboxamide (423):

Workup

  1. customto prepare
  2. filtrationfiltered (Gelman Acrodisc CR PTFE 0.45 micron)
  3. concentrationconcentrated to a solid
  4. dissolutionThe solid was dissolved in dichloromethane (25 mL)
  5. stirringThe reaction was stirred 1 hour at ambient temperature
  6. customChromatography of the crude reaction mixture through a Biotage silica cartridge (8×4 cm i.d.)
  7. customafforded three fractions
  8. customRecrystallization of fraction A from hot heptane

Sources & evidence

ORD record
ord-f3af6e52949645cb819cd5b5c64d23d1
Source dataset
uspto-grants-2006_05
Patent number
US07053104B2

Reaction notes

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