Toluene → 3-(3-Chloro-phenyl)-6-[(6-chloro-pyridin-3-yl)-(4-methoxy-benzylamino)-(3-methyl-3H-imidazol-4-yl)-methyl]-1H-quinolin-2-one

HRID 1017726Notes

Reaction equation

HRID 1017726 reaction equation
ClC1C=C([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:18]([C:26]4[CH:27]=[N:28][C:29]([Cl:32])=[CH:30][CH:31]=4)([C:20]4[N:21]([CH3:25])[CH:22]=[N:23][CH:24]=4)O)[CH:16]=3)[N:11]=[C:10]([O:33]C)[CH:9]=2)C=CC=1.S(Cl)([Cl:37])=O.[CH3:39][O:40][C:41]1[CH:48]=[CH:47][C:44]([CH2:45][NH2:46])=[CH:43][CH:42]=1.[C:49]1(C)[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1>C1COCC1>[Cl:37][C:49]1[CH:50]=[C:51]([C:9]2[C:10](=[O:33])[NH:11][C:12]3[C:17]([CH:8]=2)=[CH:16][C:15]([C:18]([C:26]2[CH:27]=[N:28][C:29]([Cl:32])=[CH:30][CH:31]=2)([NH:46][CH2:45][C:44]2[CH:47]=[CH:48][C:41]([O:40][CH3:39])=[CH:42][CH:43]=2)[C:20]2[N:21]([CH3:25])[CH:22]=[N:23][CH:24]=2)=[CH:14][CH:13]=3)[CH:52]=[CH:53][CH:54]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 24386Thionyl ChlorideHCID 754524-MethoxybenzylamineHCID 12016674[4-(3-chloro-phenyl)-2-methoxy-quinolin-6-yl]-(6-chloro-pyridin-3-yl)-(3-methyl-3H-imidazol-4-yl)-methanol

Product 1

HCID 867585963-(3-Chloro-phenyl)-6-[(6-chloro-pyridin-3-yl)-(4-methoxy-benzylamino)-(3-methyl-3H-imidazol-4-yl)-methyl]-1H-quinolin-2-oneYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
85 °C

Procedure

To [4-(3-chloro-phenyl)-2-methoxy-quinolin-6-yl]-(6-chloro-pyridin-3-yl)-(3-methy-3H -imidazol-4-yl)-methanol (1.08 g, 2.21 mmol) in toluene (8.5 ml) under an atmosphere of dry N2 was added thionyl chloride (1.61 ml, 22.06 mmol) dropwise. The reaction mixture was heated at 85° C. for 15 hours. Solvent and the excess thionyl chloride were removed under reduced pressure. The crude chloride was taken up in toluene and concentrated under vacuum. The resulting solid was dissolved in THF (10 ml) and to this solution at −78° C. was added p-methoxybenzylamine (1.44 ml, 11.03 mmol) in THF (2 ml). The reaction mixture was stirred at −78° C. for 3 hours under an atmosphere of N2 for 3 hours. After removal of THF, the product mixture was partitioned between CHCl3 and water. The organic layer was washed, dried over MgSO4 and concentrated under vacuum to give the crude product. It was chromatographed on silica gel with MeOH—CHCl3—NH4OH (2:98:0.1) as eluents to afford the title compound of Example 5A (0.482 g, 52% yield).

Workup

  1. customSolvent and the excess thionyl chloride were removed under reduced pressure
  2. concentrationconcentrated under vacuum
  3. dissolutionThe resulting solid was dissolved in THF (10 ml) and to this solution at −78° C.
  4. customAfter removal of THF
  5. customthe product mixture was partitioned between CHCl3 and water
  6. washThe organic layer was washed
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated under vacuum
  9. customto give the crude product
  10. customIt was chromatographed on silica gel with MeOH—CHCl3—NH4OH (2:98:0.1) as eluents

Sources & evidence

ORD record
ord-325353fce1284c44adaafbd422de238b
Source dataset
uspto-grants-2002_11
Patent number
US06479513B2

Reaction notes

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