Hydrochloric Acid → (+)-6-[Amino-(6-Chloro-Pyridin-3-yl)-(3-Methyl-3H-Imidazol-4-yl)-Methyl]-4-(3-Chloro-Phenyl)-1-Cyclopropylmethyl-1H-Quinolin-2-One

HRID 1936319Notes

Reaction equation

HRID 1936319 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:18]([C:35]4[CH:36]=[N:37][C:38]([Cl:41])=[CH:39][CH:40]=4)([N:25]=CC4C=CC(OC)=CC=4)[C:19]4[N:20]([CH3:24])[CH:21]=[N:22][CH:23]=4)[CH:16]=3)[N:11]([CH2:42][CH:43]3[CH2:45][CH2:44]3)[C:10](=[O:46])[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.Cl.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>C1COCC1>[NH2:25][C:18]([C:35]1[CH:36]=[N:37][C:38]([Cl:41])=[CH:39][CH:40]=1)([C:19]1[N:20]([CH3:24])[CH:21]=[N:22][CH:23]=1)[C:15]1[CH:16]=[C:17]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH2:42][CH:43]1[CH2:44][CH2:45]1)[C:10](=[O:46])[CH:9]=[C:8]2[C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 120507314-(3-chloro-phenyl)-6-[(6-chloro-pyridin-3-yl)-[(4-methoxy-benzylidene)-amino]-(3-methyl-3H-imidazol-4-yl)-methyl]-1-cyclopropylmethyl-1H-quinolin-2-one

Product 1

HCID 9849901(+)-6-[Amino-(6-Chloro-Pyridin-3-yl)-(3-Methyl-3H-Imidazol-4-yl)-Methyl]-4-(3-Chloro-Phenyl)-1-Cyclopropylmethyl-1H-Quinolin-2-OneYield 91.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the title compound of Example 45, the slower moving enantiomer of 4-(3-chloro-phenyl)-6-[(6-chloro-pyridin-3-yl)-[(4-methoxy-benzylidene)-amino]-(3-methyl-3H-imidazol-4-yl)-methyl]-1-cyclopropylmethyl-1H-quinolin-2-one (141 g, 1.74 mmol) in THF (200 ml) was added 2N hydrochloric acid (20 ml) slowly. The reaction mixture was stirred at ambient temperature for 1.5 hour after which time it was cooled to 0° C. An aqueous solution of potassium carbonate was added followed by addition of ethyl acetate. After separation, the organic layer was washed with brine, dried over MgSO4 and concentrated under vacuum to give the crude product. It was chromatographed on silica gel with MeOH-CHCl3—NH4OH (1:99:0.1 to 2:98:0.1) as the eluents to afford the title compound as a white solid (0.844 g, 1.59 mmol, 90% yield). It is the faster eluting enantiomer of 6-[amino-(6-chloro-pyridin-3-yl)-(3-methyl-3H-imidazol-4-yl)-methyl]-4-(3-chloro-phenyl)-1-cyclopropylmethyl-1H-quinolin-2-one with >99% optical purity.

Workup

  1. temperaturewas cooled to 0° C
  2. customAfter separation
  3. washthe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated under vacuum
  6. customto give the crude product
  7. customIt was chromatographed on silica gel with MeOH-CHCl3—NH4OH (1:99:0.1 to 2:98:0.1) as the eluents

Sources & evidence

ORD record
ord-48a298ba39a346bf8f72241a12870ca3
Source dataset
uspto-grants-2002_05
Patent number
US06388092B2

Reaction notes

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