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

HRID 17467ノート

反応式

HRID 17467 の反応式
[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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒2 回

反応条件

温度
150 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-1c8e6b17dd2c4198ac1f5d663a265b67
出典データセット
uspto-grants-2010_06
特許番号
US07737166B2

反応ノート

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