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Trifluoroacetic acid → 2-(2-(2-(2-((4-(Piperidin-2-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide

HRID 1485171
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HRID 1485171 반응식
[NH2:1][C:2](=[O:42])[CH2:3][C:4]1[CH:41]=[CH:40][CH:39]=[CH:38][C:5]=1[CH2:6][CH2:7][C:8]1[C:13]([C:14]([F:17])([F:16])[F:15])=[CH:12][N:11]=[C:10]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([CH:25]3[CH2:30][CH2:29][CH2:28][CH2:27][N:26]3C(OC(C)(C)C)=O)=[CH:21][CH:20]=2)[N:9]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[NH:26]1[CH2:27][CH2:28][CH2:29][CH2:30][CH:25]1[C:22]1[CH:23]=[CH:24][C:19]([NH:18][C:10]2[N:9]=[C:8]([CH2:7][CH2:6][C:5]3[CH:38]=[CH:39][CH:40]=[CH:41][C:4]=3[CH2:3][C:2]([NH2:1])=[O:42])[C:13]([C:14]([F:17])([F:15])[F:16])=[CH:12][N:11]=2)=[CH:20][CH:21]=1
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참가 물질

4

반응물 2

HCID 6422Trifluoroacetic acidHCID 71229344tert-Butyl 2-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

생성물 1

HCID 601645882-(2-(2-(2-((4-(Piperidin-2-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide수율 89%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

tert-Butyl 2-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I41) (0.087 g, 0.15 mmol) was dissolved in dry DCM (5 mL) under an atmosphere of nitrogen. Trifluoroacetic acid (0.351 mL, 4.58 mmol) was added to the solution and the reaction was stirred at room temperature for 22 hours. Volatiles were removed in vacuo, EtOAc (20 mL) and sat. aq. NaHCO3 (15 mL) were added to the residue and the layers were separated. The aqueous layer was extracted with EtOAc (15 mL), the combined organics were washed with water (50 mL), brine (50 mL), dried (MgSO4), filtered and concentrated in vacuo to give a pale yellow solid which was taken up in DCM (˜10 mL) and methanol (˜1 mL) and concentrated in vacuo. The process was repeated with only DCM twice to give the title compound (8) (0.064 g, 89% yield) as a pale yellow solid; 1H NMR (400 MHz, d6-DMSO) δ 10.15 (s, 1H), 8.66 (s, 1H), 7.70-7.62 (m, 2H), 7.44 (s, 1H), 7.30 (d, J=8.6 Hz, 2H), 7.26-7.12 (m, 4H), 6.92 (s, 1H), 3.54-3.47 (m, 3H), 3.15-2.97 (m, 5H), 2.71-2.59 (m, 1H), 1.84-1.76 (m, 1H), 1.67 (d, J=12.4 Hz, 1H), 1.61-1.50 (m, 1H), 1.46-1.27 (m, 3H). LCMS Method C: rt 4.84 min; m/z 484.3 [M+H]+.

후처리

  1. customVolatiles were removed in vacuo, EtOAc (20 mL) and sat. aq. NaHCO3 (15 mL)
  2. additionwere added to the residue
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with EtOAc (15 mL)
  5. washthe combined organics were washed with water (50 mL), brine (50 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a pale yellow solid which
  10. concentrationmethanol (˜1 mL) and concentrated in vacuo

출처 및 근거

ORD 기록
ord-4efd307fcd1b4158bea8295327b6f2de
출처 데이터셋
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09421205B2

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