Triethylamine → 4-Cyano-6-(3-fluorophenyl)-N,N,5-trimethyl-7-[(3S)-3-methylaminopyrrolidin-1-yl]-1,3-benzoxazole-carboxamide

HRID 17467Notes

Reaction equation

HRID 17467 reaction equation
[C:1]([C:3]1[C:8]2[N:9]=[C:10]([C:12]([N:14]([CH3:16])[CH3:15])=[O:13])[O:11][C:7]=2[C:6](F)=[C:5]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=2)[C:4]=1[CH3:25])#[N:2].C(N(CC)CC)C.[CH3:33][N:34](C)[C@H:35]1[CH2:39][CH2:38][NH:37][CH2:36]1>CS(C)=O>[C:1]([C:3]1[C:8]2[N:9]=[C:10]([C:12]([N:14]([CH3:16])[CH3:15])=[O:13])[O:11][C:7]=2[C:6]([N:37]2[CH2:38][CH2:39][C@H:35]([NH:34][CH3:33])[CH2:36]2)=[C:5]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=2)[C:4]=1[CH3:25])#[N:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 7019156(3S)-(-)-3-(Dimethylamino)pyrrolidineHCID 685853994-cyano-7-fluoro-6-(3-fluorophenyl)-N,N,5-trimethyl-1,3-benzoxazole-2-carboxamide

Product 1

HCID 685869324-Cyano-6-(3-fluorophenyl)-N,N,5-trimethyl-7-[(3S)-3-methylaminopyrrolidin-1-yl]-1,3-benzoxazole-carboxamide

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Conditions

Temperature
150 °C

Procedure

4-Cyano-7-fluoro-6-(3-fluorophenyl)-N,N,5-trimethyl-1,3-benzoxazole-2-carboxamide (I-184) (75 mg, 0.22 mmol) was dissolved in dimethyl sulfoxide (3.5 ml), then at room temperature, triethylamine (40 μl, 0.29 mmol) was added. The solution was heated at 150° C., a solution of (3S)-3-(dimethylamino)pyrrolidine (30 μl, 0.29 mmol) dissolved in dimethyl sulfoxide (1 ml) was added all at a time. The solution was stirred under nitrogen atmosphere at the same temperature for 1 hour. After cooling to room temperature, the solvent was evaporated away under reduced pressure. The residue was fractionated with chloroform and an aft aqueous saturated sodium hydrogencarbonate solution. The aqueous layer was further extracted twice with chloroform. 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 under reduced pressure, and the resulting residue was purified first by preparative TLC (eluent, chloroform:methanol=9:1) to obtain a roughly-purified form (54 mg). This was further purified by preparative TLC (eluent, chloroform:7 N ammonia-containing methanol solution=95:5), then recrystallized from diisopropyl ether to obtain the entitled compound (12 tag, 13%) as a white solid.

Workup

  1. additionwas added all at a time
  2. temperatureAfter cooling to room temperature
  3. customthe solvent was evaporated away under reduced pressure
  4. extractionThe aqueous layer was further extracted twice with chloroform
  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 under reduced pressure
  9. customthe resulting residue was purified first by preparative TLC (eluent, chloroform:methanol=9:1)
  10. customto obtain a roughly-purified form (54 mg)
  11. customThis was further purified by preparative TLC (eluent, chloroform:7 N ammonia-containing methanol solution=95:5)
  12. customrecrystallized from diisopropyl ether
  13. customto obtain the entitled compound (12 tag, 13%) as a white solid

Sources & evidence

ORD record
ord-1c8e6b17dd2c4198ac1f5d663a265b67
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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