Triethylamine → 6-Bromo-2-(1-methyl-1H-pyrazol-4-yl)-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridine

HRID 2205861ノート

反応式

HRID 2205861 の反応式
[C:1]([C:3]1[CH:4]=[N:5][N:6]([CH3:8])[CH:7]=1)#[CH:2].[Br:9][C:10]1[CH:15]=[C:14]([NH:16][S:17]([CH3:20])(=[O:19])=[O:18])[C:13](I)=[CH:12][N:11]=1.C(N(CC)CC)C>CN(C=O)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Br:9][C:10]1[N:11]=[CH:12][C:13]2[CH:2]=[C:1]([C:3]3[CH:4]=[N:5][N:6]([CH3:8])[CH:7]=3)[N:16]([S:17]([CH3:20])(=[O:19])=[O:18])[C:14]=2[CH:15]=1

参加物

7

反応物 3

HCID 8471TriethylamineHCID 511383214-Ethynyl-1-methyl-1H-pyrazoleHCID 86706267N-(2-Bromo-5-iodopyridin-4-yl)methanesulfonamide

生成物 1

HCID 867062756-Bromo-2-(1-methyl-1H-pyrazol-4-yl)-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridine収率 45.9%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

4-Ethynyl-1-methyl-1H-pyrazole (20) (4.11 g, 38.7 mmole) was dissolved in DMF (95 mL) and N-(2-bromo-5-iodopyridin-4-yl)methanesulfonamide 8 (12.18 g 32.3 mmole) was added. To the solution was added triethylamine (19.6 mL, 14.1 g 139 mmole) and copper(I) iodide (214 mg 1.12 mmole). The reaction was sealed and flushed with nitrogen. Bis(triphenylphosphine)palladium dichloride (797 mg 1.13 mmole) was added and the reaction was again flushed with nitrogen and heated at 60° C. for 105 minutes. Most of the DMF was evaporated and the residue taken up in ethyl acetate (350 ml). The solution was washed with water (3×100 mL) and brine. Each aqueous fraction was backwashed with the same 100 mL portion of ethyl acetate. The combined organics were dried and evaporated. The residue was flash chromatographed (silica) eluting with dichloromethane, 1:4 ethyl acetate:dichloromethane, 1:1 ethyl acetate:dichloromethane and ethyl acetate to give the title compound (5.19 g 45.9%). 1H-NMR (CDCl3, 500 MHz): δ 2.98 (s, 3H), 4.01 (s, 3H), 6.69 (d, J=0.95 Hz, 1H), 7.73 (s, 1H), 7.78 (s, 1H), 8.25 (t, J=0.95 Hz, 1H), 8.64 (d, J=0.95 Hz, 1H).

後処理

  1. customThe reaction was sealed
  2. customflushed with nitrogen
  3. customthe reaction was again flushed with nitrogen
  4. customMost of the DMF was evaporated
  5. washThe solution was washed with water (3×100 mL) and brine
  6. customThe combined organics were dried
  7. customevaporated
  8. customchromatographed (silica)
  9. washeluting with dichloromethane, 1:4 ethyl acetate

出典と根拠

ORDレコード
ord-4a03c7bfad664da69167b26f1a4aebe3
出典データセット
uspto-grants-2016_06
特許番号
US09371319B2

反応ノート

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