Potassium Carbonate → 4-Chloro-2-(1-oxo-6,7,8,9-tetrahydropyridazino[4,5-b]indolizin-2(1H)-yl)nicotinaldehyde

HRID 592817노트

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HRID 592817 반응식
[C:1]1(=[O:14])[C:6]2[CH:7]=[C:8]3[N:13]([C:5]=2[CH:4]=[N:3][NH:2]1)[CH2:12][CH2:11][CH2:10][CH2:9]3.Br[C:16]1[N:23]=[CH:22][CH:21]=[C:20]([Cl:24])[C:17]=1[CH:18]=[O:19].C(=O)([O-])[O-].[K+].[K+].COC1C2C(=C3C(=CC=2)C(OC)=CC=N3)N=CC=1>[Cu]I.O1CCOCC1>[Cl:24][C:20]1[C:17]([CH:18]=[O:19])=[C:16]([N:2]2[C:1](=[O:14])[C:6]3[CH:7]=[C:8]4[N:13]([C:5]=3[CH:4]=[N:3]2)[CH2:12][CH2:11][CH2:10][CH2:9]4)[N:23]=[CH:22][CH:21]=1

참가 물질

7

반응물 4

HCID 11430Potassium CarbonateHCID 104622984,7-Dimethoxy-1,10-phenanthrolineHCID 676394086,7,8,9-Tetrahydropyridazino[4,5-b]indolizin-1(2H)-oneHCID 866839142-Bromo-4-chloropyridine-3-carbaldehyde

생성물 1

HCID 866843544-Chloro-2-(1-oxo-6,7,8,9-tetrahydropyridazino[4,5-b]indolizin-2(1H)-yl)nicotinaldehyde수율 43.3%

시약·촉매·용매 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 312751,4-Dioxane용매

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온도
90 °C

실험 절차

A 100-mL single-neck round-bottomed flask equipped with a reflux condenser was charged with 1,4-dioxane (40 mL), 193e (800 mg, 3.6 mmol), 2-bromo-4-chloronicotinaldehyde (2.8 g, 12.6 mmol), and potassium carbonate (1.2 g, 8.4 mmol). After bubbling nitrogen through the resulting mixture for 30 minutes, copper(I) iodide (800 mg, 4.2 mmol) and 4,7-dimethoxy-1,10-phenanthroline (1.0 g, 4.2 mmol) were added, and the reaction mixture was heated at 90° C. for 12 h. After this time the reaction was cooled to room temperature and filtered. The filtrate was partitioned between methylene chloride (60 mL) and water (40 mL). The aqueous layer was separated and extracted with methylene chloride (3×40 mL). The combined organic layer was washed with brine (30 mL) and dried over sodium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 1:1 ethyl acetate/petroleum ether to afford 193f as a brown solid (513 mg, yield 37%). MS-ESI: [M+H]+ 329.1.

후처리

  1. customA 100-mL single-neck round-bottomed flask equipped with a reflux condenser
  2. customAfter bubbling nitrogen through the resulting mixture for 30 minutes
  3. temperatureAfter this time the reaction was cooled to room temperature
  4. filtrationfiltered
  5. customThe filtrate was partitioned between methylene chloride (60 mL) and water (40 mL)
  6. customThe aqueous layer was separated
  7. extractionextracted with methylene chloride (3×40 mL)
  8. washThe combined organic layer was washed with brine (30 mL)
  9. dry with materialdried over sodium sulfate
  10. customThe drying agent was removed by filtration
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customThe residue was purified by silica-gel column chromatography
  13. washeluting with 1:1 ethyl acetate/petroleum ether

출처 및 근거

ORD 기록
ord-97529ee18fd1477d80ed5d1c809170e0
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09238655B2

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