Acetic Anhydride → 2-(2-(2-(2-((4-(4-Acetylpiperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide

HRID 1485188노트

반응식

HRID 1485188 반응식
[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[N:19]=[C:18]([CH2:20][CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[CH2:28][C:29]([NH2:31])=[O:30])[C:17]([C:32]([F:35])([F:34])[F:33])=[CH:16][N:15]=3)=[CH:9][CH:8]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.C1C[O:39][CH2:38][CH2:37]1.C(N(CC)CC)C.C(OC(=O)C)(=O)C>C(Cl)Cl.CN(C=O)C>[C:38]([N:4]1[CH2:5][CH2:6][N:1]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[N:19]=[C:18]([CH2:20][CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[CH2:28][C:29]([NH2:31])=[O:30])[C:17]([C:32]([F:33])([F:35])[F:34])=[CH:16][N:15]=3)=[CH:9][CH:8]=2)[CH2:2][CH2:3]1)(=[O:39])[CH3:37]

참가 물질

7

반응물 4

HCID 7918Acetic AnhydrideHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 601644802-(2-(2-(2-((4-(Piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide

생성물 1

HCID 712093372-(2-(2-(2-((4-(4-Acetylpiperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide수율 87%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매2회

실험 절차

2-(2-(2-(2-((4-(Piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide (1) (0.020 g, 0.041 mmol) was dissolved in dry DCM (2 mL), dry THF (1 mL) and dry DMF (1 mL) then triethylamine (0.012 mL, 0.083 mmol) followed by acetic anhydride (0.008 mL, 0.083 mmol) were added. The reaction was then stirred at room temperature for 5 hours, the volatiles were removed in vacuo and the residue was diluted with EtOAc (15 mL) and sat. aq. NaHCO3 (10 mL). The layers were separated and the aqueous layer was extracted with EtOAc (10 mL), the combined organic layers were washed with water (10 mL), brine (10 mL), water (10 mL), brine (10 mL), dried (MgSO4), filtered and concentrated in vacuo to give a 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 after which the sample was further dried on high-vacuum to give the title compound (I3) (0.019 g, 87% yield) as an off-white solid; 1H NMR (400 MHz, d6-DMSO) δ 10.01 (s, 1H), 8.61 (s, 1H), 7.63-7.56 (m, 2H), 7.44 (s, 1H), 7.26-7.13 (m, 4H), 6.98-6.90 (m, 3H), 3.61-3.54 (m, 4H), 3.50 (s, 2H), 3.13-2.95 (m, 8H), 2.04 (s, 3H). LCMS Method C: rt 5.62 min; m/z 527.2 [M+H]+.

후처리

  1. additionwere added
  2. customthe volatiles were removed in vacuo
  3. additionthe residue was diluted with EtOAc (15 mL) and sat. aq. NaHCO3 (10 mL)
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with EtOAc (10 mL)
  6. washthe combined organic layers were washed with water (10 mL), brine (10 mL), water (10 mL), brine (10 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give a solid which
  11. concentrationmethanol (˜1 mL) and concentrated in vacuo
  12. customwas further dried on high-vacuum

출처 및 근거

ORD 기록
ord-f4ec4276ce474c9f9e2205cb74549e60
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09421205B2

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