Ammonium Chloride → HCID 22465395, compound

HRID 50180Notes

Reaction equation

HRID 50180 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([O:12][CH3:13])[CH:6]=[C:5]2[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=1.[Li].CON(C)[C:25]([C:27]1[S:28][C:29]([Cl:32])=[CH:30][CH:31]=1)=[O:26].[Cl-].[NH4+]>C1COCC1>[Cl:20][C:16]1[CH:15]=[C:14]([C:5]2[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([C:25]([C:27]4[S:28][C:29]([Cl:32])=[CH:30][CH:31]=4)=[O:26])[CH:3]=3)[N:8]=[C:7]([O:12][CH3:13])[CH:6]=2)[CH:19]=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 3028194LithiumHCID 120166726-Bromo-4-(3-chlorophenyl)-2-methoxyquinolineHCID 60644866HCID 60644866, compound

Product 1

HCID 22465395HCID 22465395, compoundYield 46.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 6-bromo-4-(3-chloro-phenyl)-2-methoxy-quinoline (500 mg, 1.43 mmol) in THF (2 ml) was added n-buthyl lithium (2.5 M in hexane, 0.63 ml, 1.58 mmol) dropwise at −78° C. under an atmosphere of dry N2. After stirring at −78° C. for 30 minutes, a solution of 5-chloro-thiophene-2-carboxylic acid methoxy-methyl-amide (440 mg, 2.15 mmol) in THF (1 ml) was added. The reaction mixture was allowed to warm to ambient temperature and stirred for 15 hours. To the mixture was added a saturated aqueous solution of ammonium chloride at 0° C. THF was removed from the resulting heterogeneous solution. The aqueous mixture was extracted with chloroform (CHCl3). The organic layer was washed with brine, dried over MgSO4 and concentrated under vacuum to yield the crude product. It was chromatographed on silica gel with MeOH—CHCl3—NH4OH (2:98:0.2 to 5:95:0.5) as eluents to afford the title compound of example 40A (273.5 mg, 46% yield).

Workup

  1. temperatureto warm to ambient temperature
  2. stirringstirred for 15 hours
  3. customTHF was removed from the resulting heterogeneous solution
  4. extractionThe aqueous mixture was extracted with chloroform (CHCl3)
  5. washThe organic layer was washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated under vacuum
  8. customto yield the crude product
  9. customIt was chromatographed on silica gel with MeOH—CHCl3—NH4OH (2:98:0.2 to 5:95:0.5) as eluents

Sources & evidence

ORD record
ord-6fc816794f1943ad94d6a8cd6290a085
Source dataset
uspto-grants-2004_03
Patent number
US06710209B2

Reaction notes

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