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

HRID 17529Notes

Reaction equation

HRID 17529 reaction equation
[C:1]([C:5]1[O:6][C:7]2[C:13]([C:14]#[N:15])=[C:12]([CH3:16])[C:11](C3C=CC=CC=3)=[C:10](F)[C:8]=2[N:9]=1)([CH3:4])([CH3:3])[CH3:2].C(N([CH2:29][CH3:30])CC)C.[CH3:31][N:32]([CH3:38])[C@H:33]1[CH2:37][CH2:36][NH:35][CH2:34]1.C(=O)([O-])O.[Na+]>CS(C)=O.C(OCC)(=O)C>[C:1]([CH:5]1[N:9]=[C:8]2[C:10]([N:35]3[CH2:36][CH2:37][C@H:33]([N:32]([CH3:38])[CH3:31])[CH2:34]3)=[CH:11][C:12]([CH3:16])([C:30]3[CH:29]=[CH:10][CH:8]=[CH:7][CH:13]=3)[C:13]([C:14]#[N:15])=[C:7]2[O:6]1)([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 7019156(3S)-(-)-3-(Dimethylamino)pyrrolidineHCID 68584886HCID 68584886, compound

Product 1

HCID 685848532-tert-Butyl-4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-methyl-6-phenyl-1,3-benzoxazole-7-carbonitrileYield 87%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

2-tert-Butyl-4-fluoro-6-methyl-5-phenyl-1,3-benzoxazole-7-carbonitrile (I-239) (105 mg, 0.34 mmol) was dissolved in dimethyl sulfoxide (2 ml), and at room temperature, triethylamine (95 μl, 0.68 mmol) and (3S)-3-(dimethylamino)pyrrolidine (65 μl, 0.51 mmol) were added. The solution was stirred under nitrogen atmosphere at 90° C. for 6 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 with ethyl acetate. The organic layers were combined, washed with saturated brine, then 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 middle-pressure liquid chromatography (eluent, chloroform:methanol=98:2) to obtain the entitled compound (119 mg, 87%) as a pale yellow solid.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe reaction liquid
  3. extractionThe aqueous layer was further extracted 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 middle-pressure liquid chromatography (eluent, chloroform:methanol=98:2)

Sources & evidence

ORD record
ord-64761abc99b847f49d8543de2f6a3e16
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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