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

HRID 2205859노트

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HRID 2205859 반응식
[Cl:1][C:2]1[CH:7]=[C:6]([NH:8]S(C)(=O)=O)[C:5](I)=[CH:4][N:3]=1.[C:14]([C:16]1[CH:17]=[N:18][N:19](C(OC(C)(C)C)=O)[CH:20]=1)#[CH:15].C(N(CC)CC)C.C1CCN2C(=NCCC2)CC1.[NH4+].[Cl-]>CN(C=O)C.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.[Cu](I)I>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[CH:15]=[C:14]([C:16]3[CH:17]=[N:18][NH:19][CH:20]=3)[NH:8][C:6]=2[CH:7]=1

참가 물질

9

반응물 5

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene2회HCID 45382264tert-butyl 4-ethynyl-1H-pyrazole-1-carboxylateHCID 86706272N-(2-Chloro-5-iodopyridin-4-yl)methanesulfonamide

생성물 1

HCID 867062746-Chloro-2-(1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine수율 71.1%

시약·촉매·용매 3

HCID 83717Copper iodide촉매HCID 178418476HCID 178418476, 화합물촉매HCID 6228Dimethylformamide용매

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온도
60 °C

실험 절차

Bis(triphenylphosphine)palladium dichloride (23.30 mg, 0.033 mmol) was added to a solution of N-(2-chloro-5-iodopyridin-4-yl)methanesulfonamide (14) (276.0 mg, 0.83 mmol), tert-butyl 4-ethynyl-1H-pyrazole-1-carboxylate (4) (239.0 mg, 1.24 mmol), triethylamine (521 μL, 3.73 mmol) and copper iodide (7.90 mg, 0.041 mmol) in anhydrous DMF (3.0 mL). The reaction mixture was heated at 60° C. for 1 h under microwave irradiation (absorption:normal). To this reaction mixture, DBU (0.51 mL, 3.36 mmol) was added and the microwave vial was placed in an oil-bath preheated at 100° C., and then stirred at this temperature for 2.5 h. More DBU (0.08 mL) was added and stirring was continued at this temperature for an additional 45 min. The reaction mixture was poured in to 1M aqueous NH4Cl (30 mL), extracted with EtOAc (3×50 mL). The combined organics were washed with brine (2×30 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was triturated with dichloromethane (8.0 mL); the precipitate was collected by filtration and washed with dichloromethane to afford the product as a light brown solid, (0.129 g, 71%). 1H-NMR (500 MHz, DMSO-d6) 6.72 (dd, J=0.5, 1.5 Hz, 1H), 7.33 (t, J=0.85 Hz, 1H), 8.00 (br s, 1H), 8.24 (br s, 1H), 8.51 (s, 1H), 11.87 (s, 1H), 13.09 (s, 1H).

후처리

  1. customthe microwave vial was placed in an oil-bath
  2. custompreheated at 100° C.
  3. stirringstirring
  4. waitwas continued at this temperature for an additional 45 min
  5. extractionextracted with EtOAc (3×50 mL)
  6. washThe combined organics were washed with brine (2×30 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was triturated with dichloromethane (8.0 mL)
  11. filtrationthe precipitate was collected by filtration
  12. washwashed with dichloromethane

출처 및 근거

ORD 기록
ord-3605ce2fe9624ce89fb6aee155d1d141
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09371319B2

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