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

HRID 2278898노트

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HRID 2278898 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-]>CO.C1COCC1.CCOC(C)=O.[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 2

HCID 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 80%

시약·촉매·용매 4

HCID 23994Zinc촉매HCID 887Methanol용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

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온도
0 °C

실험 절차

A solution of crude 2-ethyl-3-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)-6-nitropyridine (1.280 g, 3.93 mmol) in MeOH (15 mL) and THF (15 mL) was treated with NH4Cl (8.42 g, 157 mmol), cooled to 0° C., treated portion-wise with zinc dust (2.57 g, 39.3 mmol), warmed to RT as the cooling bath expired and stirred overnight. The mixture was diluted with EtOAc, the solids removed via filtration through diatomaceous earth, washed with warm 2:1 EtOAc/MeOH and the filtrate concentrated to dryness. The residue was treated with EtOAc, heated to reflux, cooled to RT and the solids removed via filtration. The filtrate was again treated with EtOAc, heated to reflux and the solid collected via hot filtration. The filtrate was concentrated to dryness, purified via silica gel chromatography (MeOH/EtOAc) and combined with the above-isolated solid to afford 6-ethyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-amine (929 mg, 80%). 1H NMR (400 MHz, DMSO-d6): δ 8.30 (d, J=5.8 Hz, 1 H), 8.22 (s, 1 H), 7.93 (s, 1 H), 7.18 (d, J=8.7 Hz, 1 H), 7.12 (d, J=2.4 Hz, 1 H), 6.51 (dd, J=5.7, 2.4 Hz, 1 H), 6.36 (d, J=8.7 Hz, 1 H), 5.97 (s, 2 H), 3.84-3.83 (m, 3 H), 2.39 (q, J=7.6 Hz, 2 H), 1.04 (t, J=7.5 Hz, 3 H); MS (ESI) m/z: 296.1 (M+H+).

후처리

  1. temperaturewarmed to RT as the cooling bath
  2. customthe solids removed via filtration through diatomaceous earth
  3. washwashed
  4. temperaturewith warm 2:1 EtOAc/MeOH
  5. concentrationthe filtrate concentrated to dryness
  6. additionThe residue was treated with EtOAc
  7. temperatureheated
  8. temperatureto reflux
  9. temperaturecooled to RT
  10. customthe solids removed via filtration
  11. additionThe filtrate was again treated with EtOAc
  12. temperatureheated
  13. temperatureto reflux
  14. filtrationthe solid collected via hot filtration
  15. concentrationThe filtrate was concentrated to dryness
  16. custompurified via silica gel chromatography (MeOH/EtOAc)

출처 및 근거

ORD 기록
ord-9efb80208d9e4da4a5b7182cda58a11c
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09133183B2

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