Sarcosine → 4-Chloro-2-(4-oxo-7,8,9,10-tetrahydropyridazino[4,5-a]indolizin-3(4H)-yl)nicotinaldehyde

HRID 592809노트

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HRID 592809 반응식
C(=O)([O-])[O-].[K+].[K+].[CH:7]1[C:12]2=[C:13]3[N:18]([CH:19]=[C:11]2[C:10](=[O:20])[NH:9][N:8]=1)[CH2:17][CH2:16][CH2:15][CH2:14]3.Br[C:22]1[N:29]=[CH:28][CH:27]=[C:26]([Cl:30])[C:23]=1[CH:24]=[O:25].N(CC(O)=O)C>[Cu]Br.O1CCOCC1>[Cl:30][C:26]1[C:23]([CH:24]=[O:25])=[C:22]([N:9]2[C:10](=[O:20])[C:11]3=[CH:19][N:18]4[C:13]([CH2:14][CH2:15][CH2:16][CH2:17]4)=[C:12]3[CH:7]=[N:8]2)[N:29]=[CH:28][CH:27]=1

참가 물질

7

반응물 4

HCID 1088SarcosineHCID 11430Potassium CarbonateHCID 866839142-Bromo-4-chloropyridine-3-carbaldehydeHCID 866843517,8,9,10-Tetrahydropyridazino[4,5-a]indolizin-4(3H)-one

생성물 1

HCID 866843524-Chloro-2-(4-oxo-7,8,9,10-tetrahydropyridazino[4,5-a]indolizin-3(4H)-yl)nicotinaldehyde수율 30%

시약·촉매·용매 2

HCID 24593copper(I) bromide촉매HCID 312751,4-Dioxane용매

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온도
95 °C

실험 절차

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 1,4-dioxane (50 mL), potassium carbonate (1.5 g, 10.6 mmol), 7,8,9,10-tetrahydropyridazino[4,5-a]indolizin-4(3H)-one 192b (1.0 g, 5.3 mmol), and 2-bromo-4-chloronicotinaldehyde (3.5 g, 15.9 mmol). After bubbling nitrogen through the resulting mixture for 30 minutes, copper(I) bromide (75.0 mg, 0.53 mmol) and sarcosine (47.0 mg, 0.53 mmol) were added, and the reaction mixture was heated at 95° 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 (3×70 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 10:1 ethyl acetate/petroleum ether to afford 192c as a brown solid (521 mg, 30%). MS-ESI: [M+H]+ 329.2.

후처리

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and 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 (3×70 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 10:1 ethyl acetate/petroleum ether

출처 및 근거

ORD 기록
ord-18c925ee2196458e8b0fc00a60671231
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09238655B2

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