Pyridine → HCID 178487899, compound

HRID 1826907Notes

Reaction equation

HRID 1826907 reaction equation
COC1C=CC(N)=CC=1.Cl.[CH3:11][O:12][C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][CH:22]=1)[N:19]=[CH:18][C:17]([C:23]([OH:25])=[O:24])=[CH:16]2.Cl.[CH3:27][C@H:28]1[CH2:33][CH2:32][C@H:31]([NH2:34])[CH2:30][CH2:29]1.N1C=CC=CC=1>S(Cl)(Cl)=O.C(OCC)C.C(N(CC)CC)C>[CH3:11][O:12][C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][CH:22]=1)[N:19]=[CH:18][C:17]([C:23]([OH:25])=[O:24])=[CH:16]2.[CH3:27][C@H:28]1[CH2:33][CH2:32][C@H:31]([NH:34][C:23]([C:17]2[CH:18]=[N:19][C:20]3[C:15]([CH:16]=2)=[CH:14][C:13]([O:12][CH3:11])=[CH:22][CH:21]=3)=[O:25])[CH2:30][CH2:29]1

Participants

9

Reactant 4

HCID 1049PyridineHCID 7732P-AnisidineHCID 69658922HCID 69658922, compoundHCID 178461307HCID 178461307, compound

Product 2

HCID 142415026-Methoxyquinoline-3-carboxylic acidHCID 178487899HCID 178487899, compoundYield 32.1%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8471TriethylamineSolventHCID 24386Thionyl ChlorideSolvent

Procedure

6-Methoxyquinoline-3-carboxylic acid was prepared from p-anisidine using the methods of Erickson (J. Med. Chem., 1979, 22, 7, 816–823). A solution of 6-methoxyquinoline-3-carboxylic acid hydrochloride (500 mg, 2.09 mmol) in thionyl chloride (25 mL) was heated at reflux for 1 hour. After this time the excess thionyl chloride was removed by distillation and the remaining solid dried under vacuum. The solid was suspended in dichloromethane (25 mL) and treated with trans-4-methylcyclohexylamine hydrochloride (368 mg, 2.46 mmol), pyridine (5 mL), and triethylamine (0.345 mL). The reaction was stirred at ambient temperature overnight. After this time the reaction mixture was diluted with diethyl ether (200 mL) and the resulting organic solution washed with 1 N NaOH (3×50 mL) and then brine (1×). The organic solution was then dried over anhydrous MgSO4, filtered, and concentrated to a solid. Chromatography of the crude product through a Biotage silica cartridge (8×4 cm i.d.) using a gradient of hexane to 50% ethyl acetate (in hexane) afforded 100 mg (16%) of 419:

Workup

  1. temperatureat reflux for 1 hour
  2. customAfter this time the excess thionyl chloride was removed by distillation
  3. customthe remaining solid dried under vacuum
  4. washthe resulting organic solution washed with 1 N NaOH (3×50 mL)
  5. dry with materialThe organic solution was then dried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to a solid

Sources & evidence

ORD record
ord-ca7cd690c11c4c708ef4223495dfc297
Source dataset
uspto-grants-2006_05
Patent number
US07053104B2

Reaction notes

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