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1,2-Dibromoethane → 7-(2,2-dimethylpropyl)-3-(2-fluorophenyl)-6-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-1,2,4-triazolo[4,3-b]pyridazine

HRID 1369439
ノート
印刷プレビュー

反応式

HRID 1369439 の反応式
BrCCBr.[CH2:5](I)[C:6]([CH3:9])([CH3:8])[CH3:7].Br[C:12]1[C:17]([O:18][CH2:19][C:20]2[N:21]([CH3:25])[N:22]=[CH:23][N:24]=2)=[N:16][N:15]2[C:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[F:35])=[N:27][N:28]=[C:14]2[CH:13]=1.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1>CN(C=O)C.[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH3:7][C:6]([CH3:9])([CH3:8])[CH2:5][C:12]1[C:17]([O:18][CH2:19][C:20]2[N:21]([CH3:25])[N:22]=[CH:23][N:24]=2)=[N:16][N:15]2[C:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[F:35])=[N:27][N:28]=[C:14]2[CH:13]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

9

反応物 4

HCID 78391,2-DibromoethaneHCID 84953Propane, 1-iodo-2,2-dimethyl-HCID 521585Tris(furan-2-yl)phosphaneHCID 154861777-bromo-3-(2-fluorophenyl)-6-(2-methyl2H-1,2,4-triazol-3-ylmethoxy)-1,2,4-triazolo[4,3-b]pyridazine

生成物 1

HCID 226098947-(2,2-dimethylpropyl)-3-(2-fluorophenyl)-6-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-1,2,4-triazolo[4,3-b]pyridazine収率 58.1%

試薬・触媒・溶媒 4

HCID 23994Zinc触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒2 回

実験手順

1,2-Dibromoethane (0.03 ml, 10 mol %) was added to a stirred suspension of acid washed zinc dust (0.45 g, 7.0 mmol) in anhydrous DMF (3 ml) at 50° C. under nitrogen. After 5 min, neopentyl iodide (1.0 ml, 7.5 mmol) was added. The mixture was stirred for 2.5 h to give a grey-green milky solution. A mixture of 7-bromo-3-(2-fluorophenyl)-6-(2-methyl2H-1,2,4-triazol-3-ylmethoxy)-1,2,4-triazolo[4,3-b]pyridazine (0.35 g, 0.866 mmol), tri-2-furylphosphine (0.08 g. 40 mol %) and tris(dibenzylideneacetone)dipalladium(0) (0.04 g, 5 mol %) in anhydrous DMF (2 ml) was stirred at 50° C. under nitrogen for 15 min followed by addition of the solution of organozinc reagent via syringe. After 2.5 h, the mixture was cooled, poured into water (100 ml) and extracted with dichloromethane (2×50 ml). The extracts were dried (Na2SO4), filtered and concentrated. Flash column chromatography on silica gel, eluting with 2% methanol-dichloromethane, gave a brown solid that was recrystallised from ethyl acetate-diethyl ether to give 7-(2,2-dimethylpropyl)-3-(2-fluorophenyl)-6-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-1,2,4-triazolo[4,3-b]pyridazine (0.199 g, 58%) as a beige powder; 1H NMR (360 MHz, CDCl3) δ0.96 (9H, s), 2.61 (2H, s), 3.83 (3H, s), 5.47 (2H, s), 7.28 (1H, dd, J=10 and 10 Hz), 7.36 (1H, dd, J=8 and 8 Hz), 7.56-7.62 (1H, m), 7.83 (1H, s), 7.86 (1H, dd, J=8 and 8 Hz), 7.90 (1H, s); MS (ES+) m/e 396 [MH]+. Anal. Found C, 59.66; H, 5.69; N. 24.41%. C20H22FN7O.0.4H2O requires C, 59.66; H, 5.71; N, 24.35%.

後処理

  1. customto give a grey-green milky solution
  2. stirringwas stirred at 50° C. under nitrogen for 15 min
  3. waitAfter 2.5 h
  4. temperaturethe mixture was cooled
  5. extractionextracted with dichloromethane (2×50 ml)
  6. dry with materialThe extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. washFlash column chromatography on silica gel, eluting with 2% methanol-dichloromethane
  10. customgave a brown solid that
  11. customwas recrystallised from ethyl acetate-diethyl ether

出典と根拠

ORDレコード
ord-9c25b03da5ae4335a063db6d088f8120
出典データセット
uspto-grants-2003_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US06579875B1

反応ノート

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