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

HRID 17458Notes

Reaction equation

HRID 17458 reaction equation
[CH:1]1([C:4]2[O:5][C:6]3[C:7](=[C:9]([C:17]#[N:18])[C:10]([CH3:16])=[C:11]([CH:14]=[CH2:15])[C:12]=3F)[N:8]=2)[CH2:3][CH2:2]1.C(N(CC)CC)C.[CH3:26][N:27]([CH3:33])[C@H:28]1[CH2:32][CH2:31][NH:30][CH2:29]1.C(=O)([O-])O.[Na+]>CS(C)=O.C(OCC)(=O)C>[CH:1]1([C:4]2[O:5][C:6]3[C:7](=[C:9]([C:17]#[N:18])[C:10]([CH3:16])=[C:11]([CH:14]=[CH2:15])[C:12]=3[N:30]3[CH2:31][CH2:32][C@H:28]([N:27]([CH3:33])[CH3:26])[CH2:29]3)[N:8]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 7019156(3S)-(-)-3-(Dimethylamino)pyrrolidineHCID 685849162-Cyclopropyl-7-fluoro-5-methyl-6-vinyl-1,3-benzoxazole-4-carbonitrile

Product 1

HCID 510421142-Cyclopropyl-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-5-methyl-6-vinyl-1,3-benzoxazole-4-carbonitrileYield 89.2%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

2-Cyclopropyl-7-fluoro-5-methyl-6-vinyl-1,3-benzoxazole-4-carbonitrile (I-180) (100 mg, 0.41 mmol) was dissolved in dimethyl sulfoxide (2 ml), then at room temperature, triethylamine (86 μl, 0.62 mmol) and (3S)-3-(dimethylamino)pyrrolidine (68 μl, 0.54 mmol) were added. The solution was stirred under nitrogen atmosphere at 90° C. for 4.5 hours. After cooling to room temperature, the reaction liquid was fractionated with ethyl acetate and an aqueous saturated sodium hydrogencarbonate solution. The aqueous layer was further 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, then the solvent was evaporated away, and the resulting residue was purified by preparative TLC (eluent, chloroform:methanol=9:1) to obtain a roughly-purified product (123 mg, 89%) as a pale brown solid. This was recrystallized from diisopropyl ether and hexane to obtain the entitled compound (79 mg) as a white solid.

Workup

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

Sources & evidence

ORD record
ord-acbba13ed54f4c7aba590ad90c9d1f0e
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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