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1-Ethylpiperazine → N-Boc-4-(4-ethyl-piperazin-1-yl)-2,6-difluoro-phenylamine

HRID 912156
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HRID 912156 반응식
C([N:8]([C:16]1[C:21]([F:22])=[CH:20][C:19](Br)=[CH:18][C:17]=1[F:24])[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])(OC(C)(C)C)=O.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.C(O[K])(C)(C)C.[CH2:60]([N:62]1[CH2:67][CH2:66][NH:65][CH2:64][CH2:63]1)[CH3:61]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[C:9]([NH:8][C:16]1[C:17]([F:24])=[CH:18][C:19]([N:65]2[CH2:66][CH2:67][N:62]([CH2:60][CH3:61])[CH2:63][CH2:64]2)=[CH:20][C:21]=1[F:22])([O:11][C:12]([CH3:13])([CH3:14])[CH3:15])=[O:10]
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참가 물질

8

반응물 4

HCID 791961-EthylpiperazineHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 59244410N,N-di-Boc-4-bromo-2,6-difluoro-phenylamineHCID 178418922HCID 178418922, 화합물

생성물 1

HCID 59244991N-Boc-4-(4-ethyl-piperazin-1-yl)-2,6-difluoro-phenylamine

시약·촉매·용매 3

HCID 167845
palladium(II) acetate
촉매
HCID 962Water용매
HCID 1140Toluene용매

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온도
60 °C

실험 절차

To a solution of N,N-di-Boc-4-bromo-2,6-difluoro-phenylamine (9.0 g, 22.0 mmol) obtained in Step A, palladium acetate (49 mg, 0.218 mmol), S-Phos (181 mg, 0.441 mmol), and tert-butoxy potassium (4.45 g, 39.7 mmol) in toluene (100 ml), 1-ethyl-piperazine (4.20 ml, 33.1 mmol) was added, followed by stirring at 60° C. for 14 hours. After cooling to room temperature, 100 ml of water was added, followed by extraction with ethyl acetate (100 ml×2). 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=100/1 to 10/1), whereby the desired compound was obtained (2.4 g, 32%).

후처리

  1. temperatureAfter cooling to room temperature
  2. extractionfollowed by extraction with ethyl acetate (100 ml×2)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. distillationthe solvent was distilled off under reduced pressure
  5. customThis was purified by silica gel column chromatography (dichloromethane/methanol=100/1 to 10/1), whereby the desired compound
  6. customwas obtained (2.4 g, 32%)

출처 및 근거

ORD 기록
ord-335e92d9ad294904a1fbd1086ea3c3d3
출처 데이터셋
uspto-grants-2011_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08022205B2

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