1-Propanol → 1-[4-amino-2-ethyl-7-(6-fluoropyridin-3-yl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)-2-methylpropan-2-ol

HRID 598029

반응식

HRID 598029 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][N:3]=1.[NH2:11][C:12]1[C:21]2[N:22]=[C:23]([CH2:30][CH3:31])[N:24]([CH2:25][C:26]([CH3:29])([OH:28])[CH3:27])[C:20]=2[C:19]2[N:18]=[CH:17][C:16](Br)=[CH:15][C:14]=2[N:13]=1.C(O)CC.C(=O)([O-])[O-].[Na+].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[NH2:11][C:12]1[C:21]2[N:22]=[C:23]([CH2:30][CH3:31])[N:24]([CH2:25][C:26]([CH3:27])([OH:28])[CH3:29])[C:20]=2[C:19]2[N:18]=[CH:17][C:16]([C:5]3[CH:4]=[N:3][C:2]([F:1])=[CH:7][CH:6]=3)=[CH:15][C:14]=2[N:13]=1

참가 물질

8

반응물 4

HCID 10311-PropanolHCID 10340Sodium CarbonateHCID 2783397(6-Fluoropyridin-3-yl)boronic acidHCID 589706911-(4-amino-7-bromo-2-ethyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)-2-methylpropan-2-ol

생성물 1

HCID 589706971-[4-amino-2-ethyl-7-(6-fluoropyridin-3-yl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)-2-methylpropan-2-ol수율 73.6%

시약·촉매·용매 3

HCID 11776Triphenylphosphine촉매HCID 167845palladium(II) acetate촉매HCID 962Water용매2회

실험 절차

2-Fluoropyridine-5-boronic acid (0.468 g, 3.32 mmol) was added to 1-(4-amino-7-bromo-2-ethyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)-2-methylpropan-2-ol (1.1 g, 3.0 mmol) and 1-propanol (10 mL). The mixture was degassed and backfilled with nitrogen. Triphenylphosphine (23.8 mg, 0.0900 mmol), aqueous sodium carbonate (4.53 mL of 2 M), and water (2 mL) were added followed by palladium (II) acetate (6.8 mg, 0.030 mmol). The yellow suspension was heated at reflux for two hours. Water (20 mL) was added, and the 1-propanol was removed under reduced pressure. The remaining mixture was extracted with chloroform (2×100 mL). The combined extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was triturated with acetonitrile and isolated by filtration to provide 0.84 g of 1-[4-amino-2-ethyl-7-(6-fluoropyridin-3-yl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)-2-methylpropan-2-ol as a white powder, mp 250-251° C.

후처리

  1. customThe mixture was degassed
  2. temperatureThe yellow suspension was heated
  3. temperatureat reflux for two hours
  4. customthe 1-propanol was removed under reduced pressure
  5. extractionThe remaining mixture was extracted with chloroform (2×100 mL)
  6. washThe combined extracts were washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product was triturated with acetonitrile
  11. customisolated by filtration

출처 및 근거

ORD 기록
ord-a51a4eab74e545798ee940f8ed680196
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07897609B2

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