4,7-Dimethoxy-1,10-phenanthroline → 2-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehyde

HRID 407614노트

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HRID 407614 반응식
Br[C:2]1[N:9]=[CH:8][CH:7]=[C:6]([Cl:10])[C:3]=1[CH:4]=[O:5].[C:11]([C:15]1[CH:16]=[C:17]2[C:22](=[C:23]([F:25])[CH:24]=1)[C:21](=[O:26])[NH:20][N:19]=[CH:18]2)([CH3:14])([CH3:13])[CH3:12].COC1C2C(=C3C(=CC=2)C(OC)=CC=N3)N=CC=1>O1CCOCC1.[Cu]I>[C:11]([C:15]1[CH:16]=[C:17]2[C:22](=[C:23]([F:25])[CH:24]=1)[C:21](=[O:26])[N:20]([C:2]1[N:9]=[CH:8][CH:7]=[C:6]([Cl:10])[C:3]=1[CH:4]=[O:5])[N:19]=[CH:18]2)([CH3:14])([CH3:12])[CH3:13]

참가 물질

6

반응물 3

HCID 104622984,7-Dimethoxy-1,10-phenanthrolineHCID 594737656-(tert-Butyl)-8-fluorophthalazin-1(2H)-oneHCID 866839142-Bromo-4-chloropyridine-3-carbaldehyde

생성물 1

HCID 866839152-(6-tert-Butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-chloronicotinaldehyde수율 25%

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

Into a solution of 2-bromo-4-chloronicotinaldehyde 103a (446 mg, 2.05 mmol), 6-tert-butyl-8-fluorophthalazin-1(2H)-one 101h (300 mg, 1.36 mmol) in dioxane (50 mL) was added KAcO (267 mg, 2.72 mmol), CuI(259 mg, 1.36 mmol), and 4,7-dimethoxy-1,10-phenanthroline (327 mg, 1.36 mmol). After bubbling nitrogen through the resulting solution for 30 min, the mixture was stirred at 90° C. for 10 h. It was allowed to cool down to room temperature and H2O (100 mL) was added. The aqueous layer was separated and extracted with ethyl acetate (2×200 mL). The combined organic layer was washed with brine (100 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 on flash column eluting with 10:1 PE/EA to afford 103b (120 mg, 25%). LCMS: [M+H]+ 360. 1H NMR (500 MHz, CDCl3) δ 10.36 (s, 1H), 8.69 (d, J=5.5, 1H), 8.28 (d, J=2.0, 1H), 7.28-7.56 (m, 3H), 1.49 (s, 9H)

후처리

  1. customAfter bubbling nitrogen through the resulting solution for 30 min
  2. temperatureto cool down to room temperature
  3. additionH2O (100 mL) was added
  4. customThe aqueous layer was separated
  5. extractionextracted with ethyl acetate (2×200 mL)
  6. washThe combined organic layer was washed with brine (100 mL)
  7. dry with materialdried over sodium sulfate
  8. customThe drying agent was removed by filtration
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customThe residue was purified on flash column
  11. washeluting with 10:1 PE/EA

출처 및 근거

ORD 기록
ord-b7c1f135df05428d82f38a8b06e0a0d0
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08754077B2

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