1-Hydroxybenzotriazole → [3,5-Difluoro-4-(4-methoxy-benzylamino)-phenyl]-(4-ethyl-piperazin-1-yl)-methanone

HRID 912166ノート

反応式

HRID 912166 の反応式
[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([F:21])[C:10]=1[NH:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=1)[C:5]([OH:7])=O.C(N(C(C)C)C(C)C)C.C1C=CC2N(O)N=NC=2C=1.[CH2:41]([N:43]1[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1)[CH3:42]>C(#N)C>[F:21][C:9]1[CH:8]=[C:4]([C:5]([N:46]2[CH2:47][CH2:48][N:43]([CH2:41][CH3:42])[CH2:44][CH2:45]2)=[O:7])[CH:3]=[C:2]([F:1])[C:10]=1[NH:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=1

参加物

6

反応物 4

HCID 757711-Hydroxybenzotriazole2 回HCID 791961-EthylpiperazineHCID 81531Diisopropylethylamine2 回HCID 592447773,5-Difluoro-4-(4-methoxy-benzylamino)-benzoic acid

生成物 1

HCID 59244390[3,5-Difluoro-4-(4-methoxy-benzylamino)-phenyl]-(4-ethyl-piperazin-1-yl)-methanone収率 99%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

To a solution of 3,5-difluoro-4-(4-methoxy-benzylamino)-benzoic acid (9.00 g, 30.7 mmol) obtained in Step B in acetonitrile (150 ml), N-ethyldiisopropylamine (16.0 ml, 92.1 mmol), HOBt (4.15 g, 30.7 mmol) and WSCI (5.88 g, 30.7 mmol) were added, followed by stirring at room temperature for 10 minutes. To this, 1-ethyl-piperazine (4.68 ml, 368 mmol) was added, followed by stirring at room temperature for 62 hours. N-Ethyldiisopropylamine (5.35 ml, 30.7 mmol), HOBt (2.07 g, 15.3 mmol) and WSCI (2.94 g, 15.3 mmol) were added at room temperature, followed by stirring for 22 hours. The solvent was distilled off under reduced pressure, followed by dissolution in ethyl acetate (300 ml), which was washed with saturated aqueous sodium chloride solution (100 ml) and saturated sodium hydrogencarbonate aqueous solution (100 ml). Subsequently, the organic layer was dried over sodium sulfate, and the solvent was distilled off under reduced pressure. This was purified by silica gel column chromatography (dichloromethane/methanol=50/1 to 25/1), to obtain the desired compound as a brown oil (11.8 g, 99%).

後処理

  1. stirringby stirring at room temperature for 62 hours
  2. stirringby stirring for 22 hours
  3. distillationThe solvent was distilled off under reduced pressure
  4. dissolutionfollowed by dissolution in ethyl acetate (300 ml)
  5. washwhich was washed with saturated aqueous sodium chloride solution (100 ml) and saturated sodium hydrogencarbonate aqueous solution (100 ml)
  6. dry with materialSubsequently, the organic layer was dried over sodium sulfate
  7. distillationthe solvent was distilled off under reduced pressure
  8. customThis was purified by silica gel column chromatography (dichloromethane/methanol=50/1 to 25/1)

出典と根拠

ORDレコード
ord-85b18fc9a55c4c8f98deee654d86dd17
出典データセット
uspto-grants-2011_09
特許番号
US08022205B2

反応ノート

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