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

HRID 17404Notes

Reaction equation

HRID 17404 reaction equation
[CH2:1]([N:3]([CH2:23][CH3:24])[C:4]1[O:5][C:6]2[C:7](=[C:9]([C:21]#[N:22])[C:10]([CH3:20])=[C:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:12]=2F)[N:8]=1)[CH3:2].C(N(CC)CC)C.[CH3:32][N:33]([CH3:39])[C@H:34]1[CH2:38][CH2:37][NH:36][CH2:35]1.C(OCC)(=O)C>CS(C)=O.[Cl-].[Na+].O>[CH2:1]([N:3]([CH2:23][CH3:24])[C:4]1[O:5][C:6]2[C:7](=[C:9]([C:21]#[N:22])[C:10]([CH3:20])=[C:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:12]=2[N:36]2[CH2:37][CH2:38][C@H:34]([N:33]([CH3:39])[CH3:32])[CH2:35]2)[N:8]=1)[CH3:2]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 7019156(3S)-(-)-3-(Dimethylamino)pyrrolidineHCID 685846722-(Diethylamino)-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile

Product 1

HCID 510393152-(diethylamino)-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrileYield 65.9%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
150 °C

Procedure

2-(Diethylamino)-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile (I-133) (78 mg, 0.24 mmol) was dissolved in dimethyl sulfoxide (2 ml) in a sealed tube, then triethylamine (67 μl, 0.48 mmol) and (3S)-3-(dimethylamino)pyrrolidine (61 μl, 0.48 mmol) were added. The reaction system was heated at 150° C. for 4.5 hours and then at 100° C. for 60 hours. After cooling to room temperature, the reaction liquid was fractionated with ethyl acetate and saturated brine. The aqueous layer was separated, and this was extracted twice with ethyl acetate. The organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The insoluble matter was separated by filtration, the solvent was evaporated away, and the resulting residue was purified by preparative TLC (eluent, chloroform:methanol=92:8) to obtain the entitled compound (66 mg, 65%) as a brown solid.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe reaction liquid
  3. customThe aqueous layer was separated
  4. extractionthis was extracted twice with ethyl acetate
  5. washwashed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe insoluble matter was separated by filtration
  8. customthe solvent was evaporated away
  9. customthe resulting residue was purified by preparative TLC (eluent, chloroform:methanol=92:8)

Sources & evidence

ORD record
ord-f567b4c996f34317b6db32c71d46e6c5
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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