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

HRID 2205861노트

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HRID 2205861 반응식
[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

참가 물질

7

반응물 3

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

생성물 1

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

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418476HCID 178418476, 화합물촉매HCID 6228Dimethylformamide용매

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온도
60 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-4a03c7bfad664da69167b26f1a4aebe3
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09371319B2

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