Ethyl Acetate → 6-Ethyl-5-[[2-(1-methyl-1h-pyrazol-4-yl)-4-pyridinyl]oxy]-2-pyridinamine

HRID 1049248노트

반응식

HRID 1049248 반응식
[CH2:1]([C:3]1[C:8]([O:9][C:10]2[CH:15]=[CH:14][N:13]=[C:12]([C:16]3[CH:17]=[N:18][N:19]([CH3:21])[CH:20]=3)[CH:11]=2)=[CH:7][CH:6]=[C:5]([N+:22]([O-])=O)[N:4]=1)[CH3:2].[NH4+].[Cl-].CCOC(C)=O>CO.C1COCC1.[Zn]>[CH2:1]([C:3]1[N:4]=[C:5]([NH2:22])[CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]([C:16]2[CH:17]=[N:18][N:19]([CH3:21])[CH:20]=2)[CH:11]=1)[CH3:2]

참가 물질

7

반응물 3

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 904036202-Ethyl-3-[[2-(1-methyl-1h-pyrazol-4-yl)-4-pyridinyl]oxy]-6-nitropyridine

생성물 1

HCID 904038036-Ethyl-5-[[2-(1-methyl-1h-pyrazol-4-yl)-4-pyridinyl]oxy]-2-pyridinamine수율 51.3%

시약·촉매·용매 3

HCID 23994Zinc촉매HCID 887Methanol용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
0 °C

실험 절차

A mixture of crude 2-ethyl-3-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)-6-nitropyridine (1.038 g, 3.19 mmol) in MeOH (12 mL) and THF (12 mL) was treated with NH4Cl (6.83 g, 128 mmol), cooled to 0° C., treated portion-wise with zinc dust (2.08 g, 31.9 mmol) and stirred overnight as the cooling bath expired. The mixture was treated with EtOAc, the solids removed via filtration through diatomaceous earth, washed well with warm EtOAc and the filtrate concentrated to dryness. The residue was treated with EtOAc, heated to near-reflux, filtered to remove solids and the filtrate concentrated to dryness. The collected solids were treated again with EtOAc, heated to reflux and filtered hot to afford a white solid. The concentrated filtrate was purified via silica gel chromatography (MeOH/EtOAc) and combined with the solid isolated above to afford 6-ethyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-amine (483 mg, 51%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6): δ 8.30 (d, J=5.7 Hz, 1H), 8.22 (s, 1H), 7.93 (s, 1H), 7.18-7.16 (m, 1H), 7.12 (d, J=2.4 Hz, 1H), 6.50-6.49 (m, 1H), 6.36-6.34 (m, 1H), 5.95-5.93 (m, 2H), 3.84 (s, 3H), 2.40-2.38 (m, 2H), 1.04 (t, J=7.5 Hz, 3H); MS (ESI) m/z: 296.2 (M+H+).

후처리

  1. customthe solids removed via filtration through diatomaceous earth
  2. washwashed well with warm EtOAc
  3. concentrationthe filtrate concentrated to dryness
  4. additionThe residue was treated with EtOAc
  5. temperatureheated
  6. temperatureto near-reflux
  7. filtrationfiltered
  8. customto remove solids
  9. concentrationthe filtrate concentrated to dryness
  10. additionThe collected solids were treated again with EtOAc
  11. temperatureheated
  12. temperatureto reflux
  13. filtrationfiltered hot
  14. customto afford a white solid
  15. customThe concentrated filtrate was purified via silica gel chromatography (MeOH/EtOAc)
  16. customisolated above

출처 및 근거

ORD 기록
ord-d9c848bceb954a69bd4572b66d5f643f
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09382228B2

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