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

HRID 17613Notes

Reaction equation

HRID 17613 reaction equation
[CH:1]1([C:4]2[O:5][C:6]3[C:7](=[C:9]([C:20]#[N:21])[C:10]([CH3:19])=[C:11]([N:14]4[CH:18]=[CH:17][CH:16]=[CH:15]4)[C:12]=3F)[N:8]=2)[CH2:3][CH2:2]1.C(N(CC)CC)C.[CH3:29][N:30]([CH3:36])[C@H:31]1[CH2:35][CH2:34][NH:33][CH2:32]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:20]#[N:21])[C:10]([CH3:19])=[C:11]([N:14]4[CH:18]=[CH:17][CH:16]=[CH:15]4)[C:12]=3[N:33]3[CH2:34][CH2:35][C@H:31]([N:30]([CH3:36])[CH3:29])[CH2:32]3)[N:8]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 7019156(3S)-(-)-3-(Dimethylamino)pyrrolidineHCID 685846202-Cyclopropyl-7-fluoro-5-methyl-6-(pyrrol-1-yl)-1,3-benzoxazole-4-carbonitrile

Product 1

HCID 685849722-Cyclopropyl-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-5-methyl-6-(pyrrol-1-yl)-1,3-benzoxazole-4-carbonitrileYield 71%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

2-Cyclopropyl-7-fluoro-5-methyl-6-(pyrrol-1-yl)-1,3-benzoxazole-4-carbonitrile (I-320) (28 mg, 0.10 mmol) was dissolved in dimethyl sulfoxide (2 ml), then at room temperature, triethylamine (18 μl, 0.13 mmol) and (3S)-3-(dimethylamino)pyrrolidine (17 μl, 0.13 mmol) were added, followed by stirring under nitrogen atmosphere at 100° C. for 5.5 hours. The reaction liquid was cooled to room temperature, then 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, the solvent was evaporated away, and the resulting residue was roughly purified by preparative TLC (eluent, chloroform:methanol=92:8, v/v), and the obtained solid was further purified in slurry with diisopropyl ether. This was dried at 60° C. under reduced pressure for 12 hours to obtain the entitled compound (26.5 mg, 71%) as a white solid.

Workup

  1. customThe reaction liquid
  2. temperaturewas cooled to room temperature
  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 roughly purified by preparative TLC (eluent, chloroform:methanol=92:8, v/v)
  9. customthe obtained solid was further purified in slurry with diisopropyl ether
  10. customThis was dried at 60° C. under reduced pressure for 12 hours

Sources & evidence

ORD record
ord-d513522d9c6541b6b48c02a56d32028d
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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