Sodium Carbonate → 5-(4-Methyl-pyrimidin-2-yl)-indan-1-one

HRID 1913406노트

반응식

HRID 1913406 반응식
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[C:14](=[O:18])[CH2:13][CH2:12]3)O1.Br[C:21]1[N:26]=[C:25]([CH3:27])[CH:24]=[CH:23][N:22]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O>[CH3:27][C:25]1[CH:24]=[CH:23][N:22]=[C:21]([C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[C:14](=[O:18])[CH2:13][CH2:12]3)[N:26]=1

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 109429282-Bromo-4-methylpyrimidineHCID 185417105-(tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-one

생성물 1

HCID 584384675-(4-Methyl-pyrimidin-2-yl)-indan-1-one

시약·촉매·용매 2

HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

실험 절차

To a 25 mL flask containing 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indan-1-one (SM-1a, 50.0 mg, 0.19 mmol) was added 2-bromo-4-methyl pyrimidine (33.6 mg, 0.16 mmol) and sodium carbonate (23 mg, 0.76 mmol). The mixture was dissolved in 2 mL DME and 0.5 mL water. The mixture was purged with nitrogen for 15 minutes. Pd(dppf)Cl2 (2.9 mg, 5 mol %) was added and the solution was degassed for an additional 15 minutes. The reaction was heated under reflux for 16 hours. The reaction was concentrated to dryness and was partitioned between ethyl acetate and water. The water layer was extracted with ethyl acetate and the combined organic layers were washed twice with water and once with brine. The solution was dried over anhydrous sodium sulfate, filtered and concentrated. The final product was purified by silica chromatography on a Combiflash ISCO purification system (Teledyne Corp., Lincoln, Nebr.) eluting with 0-50% ethyl acetate in heptanes. The product was obtained as a white solid (SM-1e, 8.7 mg, 20%). MS (ES+) 225.2 (M+H+). 1H NMR (CDCl3) δ 2.61 (s, 3H), 2.74-2.78 (m, 2H), 3.20 (t, 2H), 7.15 (d, 1H), 7.85 (d, 1H), 8.53 (d, 1H), 8.59 (s, 1H), 8.75 (d, 1H).

후처리

  1. customThe mixture was purged with nitrogen for 15 minutes
  2. additionPd(dppf)Cl2 (2.9 mg, 5 mol %) was added
  3. customthe solution was degassed for an additional 15 minutes
  4. temperatureThe reaction was heated
  5. temperatureunder reflux for 16 hours
  6. concentrationThe reaction was concentrated to dryness
  7. customwas partitioned between ethyl acetate and water
  8. extractionThe water layer was extracted with ethyl acetate
  9. washthe combined organic layers were washed twice with water and once with brine
  10. dry with materialThe solution was dried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe final product was purified by silica chromatography on a Combiflash ISCO purification system (Teledyne Corp., Lincoln, Nebr.)
  14. washeluting with 0-50% ethyl acetate in heptanes
  15. customThe product was obtained as a white solid (SM-1e, 8.7 mg, 20%)

출처 및 근거

ORD 기록
ord-3844b0dc6ca04abd922a0a8c604ea0d9
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08609680B2

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