Tetrahydrofuran → 7-Methoxy-N-((6-(3,4,5-trifluorophenyl)imidazo[1,2-b]pyridazin-3-yl)methyl)-1,5-naphthyridin-4-amine

HRID 219120

反応式

HRID 219120 の反応式
[F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:11]=[CH:12][C:13]3[N:14]([C:16]([CH2:19][NH2:20])=[CH:17][N:18]=3)[N:15]=2)[CH:5]=[C:6]([F:9])[C:7]=1[F:8].FC1C=C([C:30]2[CH:31]=[CH:32][C:33]3[N:34]([C:36](CO)=CN=3)[N:35]=2)C=C(F)C=1F.C(N(CC)CC)C.N([Na])=[N+]=[N-].CP(C)C.[CH2:56]1[CH2:60][O:59][CH2:58][CH2:57]1>C(Cl)Cl.O.CCOC(C)=O>[CH3:58][O:59][C:60]1[CH:56]=[C:57]2[C:33]([C:32]([NH:20][CH2:19][C:16]3[N:14]4[N:15]=[C:10]([C:4]5[CH:5]=[C:6]([F:9])[C:7]([F:8])=[C:2]([F:1])[CH:3]=5)[CH:11]=[CH:12][C:13]4=[N:18][CH:17]=3)=[CH:31][CH:30]=[N:35]2)=[N:34][CH:36]=1

参加物

10

反応物 6

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 68983TrimethylphosphineHCID 67502440(6-(3,4,5-Trifluorophenyl)imidazo[1,2-b]pyridazin-3-yl)methanolHCID 68925952(6-(3,4,5-Trifluorophenyl)imidazo[1,2-b]pyridazin-3-yl)methanamineHCID 178514644HCID 178514644、化合物2 回

生成物 1

HCID 576909397-Methoxy-N-((6-(3,4,5-trifluorophenyl)imidazo[1,2-b]pyridazin-3-yl)methyl)-1,5-naphthyridin-4-amine

試薬・触媒・溶媒 3

HCID 962Water溶媒2 回HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒2 回

実験手順

(6-(3,4,5-Trifluorophenyl)imidazo[1,2-b]pyridazin-3-yl)methanamine. To a suspension of (6-(3,4,5-trifluorophenyl)imidazo[1,2-b]pyridazin-3-yl)methanol (0.442 g, 1.6 mmol) in CH2Cl2 (5 mL) was added Mesyl-Cl (0.37 ml, 4.7 mmol) and triethylamine (0.66 ml, 4.7 mmol)-slight exotherm, place flask in water bath- and the mixture stirred at rt 1 h. The mixture was concentrated in vacuo (without heating the flask) and the residue dissolved in DMF (2 mL) and azidosodium (0.23 g, 3.5 mmol) was added in one portion. After 45 minutes, additional azidosodium (0.40 g, 6.0 mmol) was added and the mixture stirred 1 h longer. The mixture was diluted with EtOAc, washed with water, brine, (back extract aq layer) and dry organic layer over Na2SO4, filter and evaporate. The azide intermediate was dissolved in THF (4 mL) and trimethylphosphine 1M in THF (2.4 ml, 2.4 mmol) was added. The reaction mixture was stir at rt until the bubbling stops, plus an additional 2 minutes, then water (1 mL) was added. The mixture was diluted with EtOAc, washed with NaHCO3 solution, sat. NaHCO3, (back extract aq layer), then dry organic layer over Na2SO4, filter and evaporate. The residue was purified via flash chromatography using a 1% NH4OH in MeOH in CH2Cl2 gradient to afford the title compound as a tan solid. b) 7-Methoxy-N-((6-(3,4,5-trifluorophenyl)imidazo[1,2-b]pyridazin-3-yl)methyl)-1,5-naphthyridin-4-amine. The title compound was prepared according to Method D, with the addition of 1 equivalent TFA. M/Z=437.1 [M+H], calc 436.3955 for C22H15F3N6O.

後処理

  1. concentrationThe mixture was concentrated in vacuo (
  2. temperaturewithout heating the flask) and the residue
  3. dissolutiondissolved in DMF (2 mL)
  4. waitAfter 45 minutes
  5. stirringthe mixture stirred 1 h longer
  6. washwashed with water, brine
  7. filtration(back extract aq layer) and dry organic layer over Na2SO4, filter
  8. customevaporate
  9. dissolutionThe azide intermediate was dissolved in THF (4 mL)
  10. stirringThe reaction mixture was stir at rt until the bubbling
  11. washwashed with NaHCO3 solution, sat. NaHCO3
  12. filtration(back extract aq layer), then dry organic layer over Na2SO4, filter
  13. customevaporate
  14. customThe residue was purified via flash chromatography

出典と根拠

ORDレコード
ord-1a80b0b1a69c4ee5b12c675be6b5f574
出典データセット
uspto-grants-2012_06
特許番号
US08198448B2

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