Nitrogen → 3-cyclopropyl-1-((6-methylpyridin-2-yl)methyl)-4-nitro-1H-indazole

HRID 79401

반응식

HRID 79401 반응식
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[N+:11]([O-:13])=[O:12])[N:4]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[N:16]=2)[N:3]=1.[CH:22]1(B(O)O)[CH2:24][CH2:23]1.C(=O)([O-])[O-].[K+].[K+].N#N>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(C)C=CC=CC=1.O>[CH:22]1([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][C:9]=3[N+:11]([O-:13])=[O:12])[N:4]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[N:16]=3)[N:3]=2)[CH2:24][CH2:23]1

참가 물질

9

반응물 4

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 2760897Cyclopropylboronic acidHCID 672598643-Bromo-1-((6-methylpyridin-2-yl)methyl)-4-nitro-1H-indazole

생성물 1

HCID 672608093-cyclopropyl-1-((6-methylpyridin-2-yl)methyl)-4-nitro-1H-indazole수율 77.7%

시약·촉매·용매 4

HCID 11776Triphenylphosphine촉매HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 1140Toluene용매

반응 조건

온도
90 °C

실험 절차

3-Bromo-1-((6-methylpyridin-2-yl)methyl)-4-nitro-1H-indazole (10.0 g, 28.8 mmol), cyclopropylboronic acid (6.2 g, 72.0 mmol), palladium acetate (0.2 g, 0.9 mmol), triphenylphosphine (0.5 g, 1.7 mmol) and potassium carbonate (15.9 g, 115.2 mmol) were added to a mixture of H2O (50 mL) and toluene (50 mL) in a 250 mL round bottomed flask equipped with mechanical stirring, a thermal couple, a reflux condenser and a static pressure N2 line. The solution was degassed by sparging with N2 for 15 minutes and then heated with stirring under N2 at 90° C. for 18 hours. The solution was cooled to ambient temperature, treated with activated carbon, filtered through Celite®, and the filter cake was rinsed with toluene (100 mL). The filtrate was partitioned using a reparatory funnel and after extraction of the organic phase with H2O (2×50 mL) the organic layer was concentrated to dryness. The crude product was triturated with isopropyl alcohol (50 mL). The solids were collected by vacuum filtration, washed with heptane and dried under vacuum to afford 3-cyclopropyl-1-((6-methylpyridin-2-yl)methyl)-4-nitro-1H-indazole (6.9 g).

후처리

  1. customequipped with mechanical stirring
  2. customThe solution was degassed
  3. customby sparging with N2 for 15 minutes
  4. temperatureheated
  5. temperatureThe solution was cooled to ambient temperature
  6. additiontreated with activated carbon
  7. filtrationfiltered through Celite®
  8. washthe filter cake was rinsed with toluene (100 mL)
  9. customThe filtrate was partitioned
  10. extractionafter extraction of the organic phase with H2O (2×50 mL) the organic layer
  11. concentrationwas concentrated to dryness
  12. customThe crude product was triturated with isopropyl alcohol (50 mL)
  13. filtrationThe solids were collected by vacuum filtration
  14. washwashed with heptane
  15. customdried under vacuum

출처 및 근거

ORD 기록
ord-c95d17a029b84b69a73773d29fe35471
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08841455B2

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