Trifluoroacetic acid → 2-(2-(2-(2-((4-(Piperidin-3-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide

HRID 1485157노트

반응식

HRID 1485157 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][N:27](C(OC(C)(C)C)=O)[CH2:26]3)=[CH:21][CH:20]=2)[N:9]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[NH:27]1[CH2:28][CH2:29][CH2:30][CH:25]([C:22]2[CH:23]=[CH:24][C:19]([NH:18][C:10]3[N:9]=[C:8]([CH2:7][CH2:6][C:5]4[CH:38]=[CH:39][CH:40]=[CH:41][C:4]=4[CH2:3][C:2]([NH2:1])=[O:42])[C:13]([C:14]([F:17])([F:15])[F:16])=[CH:12][N:11]=3)=[CH:20][CH:21]=2)[CH2:26]1

참가 물질

4

반응물 2

HCID 6422Trifluoroacetic acidHCID 71229644tert-Butyl 3-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

생성물 1

HCID 601645862-(2-(2-(2-((4-(Piperidin-3-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide수율 72.2%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

tert-Butyl 3-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I28) (0.184 g, 0.315 mmol) was dissolved in DCM (10 mL) under an atmosphere of nitrogen. Trifluoroacetic acid (1.21 mL, 15.8 mmol) was added to the solution and the reaction was stirred at room temperature for 1 hour. Volatiles were removed in vacuo, EtOAc (100 mL) and 2 M aq. NaOH (70 mL) were added to the residue and the layers were separated. The aqueous layer was extracted with EtOAc (70 mL), the combined organics were washed with water (50 mL), brine (50 mL), dried (MgSO4), filtered and concentrated in vacuo to give a white solid. The solid was taken up in DCM (˜7 mL) and methanol (˜1 mL) and concentrated in vacuo. The process was repeated with only DCM twice to give the title compound (4) (0.110 g, 72% yield) as a white solid; 1H NMR (400 MHz, d6-DMSO) δ 10.13 (s, 1H), 8.65 (s, 1H), 7.69-7.62 (m, 2H), 7.44 (s, 1H), 7.26-7.12 (m, 6H), 6.93 (s, 1H), 3.50 (s, 2H), 3.15-3.06 (m, 2H), 3.06-2.90 (m, 4H), 2.60-2.43 (m, 3H), 1.85 (d, J=11.1 Hz, 1H), 1.69-1.61 (m, 1H), 1.61-1.41 (m, 2H). 3 Aliphatic protons obscured by residual DMSO. LCMS Method C: rt 4.81 min; m/z 484.3 [M+H]+.

후처리

  1. customVolatiles were removed in vacuo, EtOAc (100 mL) and 2 M aq. NaOH (70 mL)
  2. additionwere added to the residue
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with EtOAc (70 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 white solid
  10. concentrationmethanol (˜1 mL) and concentrated in vacuo

출처 및 근거

ORD 기록
ord-3a70b84f531d41f7be3a5fc752849226
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09421205B2

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