(3S)-(-)-3-(Dimethylamino)pyrrolidine → 7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-2-(methoxymethyl)-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile

HRID 17314

Reaction equation

HRID 17314 reaction equation
[CH3:1][N:2]([CH3:8])[C@H:3]1[CH2:7][CH2:6][NH:5][CH2:4]1.F[C:10]1[C:11]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[C:12]([CH3:24])[C:13]([C:22]#[N:23])=[C:14]2[C:18]=1[O:17][C:16]([CH2:19][O:20][CH3:21])=[N:15]2.O.C(=O)(O)[O-].[Na+]>CS(C)=O>[CH3:1][N:2]([CH3:8])[C@H:3]1[CH2:7][CH2:6][N:5]([C:10]2[C:11]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[C:12]([CH3:24])[C:13]([C:22]#[N:23])=[C:14]3[C:18]=2[O:17][C:16]([CH2:19][O:20][CH3:21])=[N:15]3)[CH2:4]1

Participants

5

Reactant 3

HCID 7019156(3S)-(-)-3-(Dimethylamino)pyrrolidineHCID 685851157-Fluoro-2-(methoxymethyl)-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrileHCID 86585896Sodium bicarbonate water

Product 1

HCID 685844727-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-2-(methoxymethyl)-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrileYield 17%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
90 °C

Procedure

(3S)-3-(Dimethylamino)pyrrolidine (76 μl, 0.60 mmol) was added to a dimethyl sulfoxide (4 ml) solution of 7-fluoro-2-(methoxymethyl)-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile (I-59) (58 mg, 0.20 mmol), followed by stirring at 90° C. for 1 hour. After cooling to room temperature, the above brown oily substance and saturated sodium bicarbonate water were added, followed by extraction three times with ethyl acetate, the organic layer was washed with saturated brine, then dried over anhydrous magnesium sulfate. After filtration and concentration under reduced pressure, the resulting residue was subjected to column chromatography, and the eluate with chloroform:methanol (50:1) was concentrated under reduced pressure, the residue was dissolved in ethyl acetate, washed twice with saturated brine, then dried over anhydrous magnesium sulfate. After filtration and concentration tinder reduced pressure, the entitled compound (39 mg, 17%) was obtained as a brown oily substance.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionfollowed by extraction three times with ethyl acetate
  3. washthe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationAfter filtration and concentration under reduced pressure
  6. concentrationthe eluate with chloroform:methanol (50:1) was concentrated under reduced pressure
  7. dissolutionthe residue was dissolved in ethyl acetate
  8. washwashed twice with saturated brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationAfter filtration and concentration tinder reduced pressure

Sources & evidence

ORD record
ord-b341d755573047dcac0d67357cf083fb
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Linked notes

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