N,N'-Dimethylethylenediamine → 6-chloro-1-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-1H-indole

HRID 522772노트

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HRID 522772 반응식
[Cl:1][C:2]1[C:10]([F:11])=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=1.Br[C:13]1[CH:14]=[N:15][N:16]([CH2:18][CH3:19])[CH:17]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CNCCNC>C1(C)C=CC=CC=1.CCCCCC>[Cl:1][C:2]1[C:10]([F:11])=[C:9]2[C:5]([CH:6]=[CH:7][N:8]2[C:13]2[CH:14]=[N:15][N:16]([CH2:18][CH3:19])[CH:17]=2)=[CH:4][CH:3]=1

참가 물질

7

반응물 4

HCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 125652014-Bromo-1-ethyl-1H-pyrazoleHCID 226127456-chloro-7-fluoro-1H-indole

생성물 1

HCID 1181041956-chloro-1-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-1H-indole수율 36%

시약·촉매·용매 2

HCID 1140Toluene용매HCID 8058Hexane용매

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온도
140 °C

실험 절차

To a stirred solution of 6-chloro-7-fluoro-1H-indole 8 (400 mg, 2.36 mmol) in toluene (10 mL) were added 4-bromo-1-ethyl-1H-pyrazole 4 (Step 3 above; 414 mg, 2.36 mmol), potassium phosphate (1.25 g, 5.91 mmol), N,N′-dimethylethylenediamine (84 mg, 0.95 mmol) and Cu(I)I (45 mg, 0.24 mmol) at RT under inert atmosphere. The resulted solution was purged with argon and sealed the tube. The reaction mixture was then heated to 140° C. for 16 h. After completion of the reaction (monitored by TLC), the reaction mixture was cooled to RT, diluted with hexane (10 mL) and filtered through a short pad of celite. The filtrate was washed with water (2×10 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude. The crude was purified (silica gel chromatography; 8-10% EtOAc/Hexanes) to afford compound 9 (224 mg, 36%) as a light brown thick liquid. 1H NMR (500 MHz, CDCl3): δ 7.64 (s, 1H), 7.61 (s, 1H), 7.31 (d, J=8.0 Hz, 1H), 7.12-7.07 (m, 2H), 6.60-6.59 (m, 1H), 4.22 (q, J=7.5 Hz, 2H), 1.55 (t, J=7.5 Hz, 3H); LC-MS (ESI): 94.7%; m/z 264.1 (M+H+); (column: X Select C-18, 50×3.0 mm, 3.5 μm); RT 3.87 min; 5 mM NH4OAc: ACN; 0.8 mL/min).

후처리

  1. customThe resulted solution was purged with argon
  2. customsealed the tube
  3. customAfter completion of the reaction (monitored by TLC)
  4. temperaturethe reaction mixture was cooled to RT
  5. filtrationfiltered through a short pad of celite
  6. washThe filtrate was washed with water (2×10 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto obtain the crude
  11. customThe crude was purified (silica gel chromatography; 8-10% EtOAc/Hexanes)

출처 및 근거

ORD 기록
ord-579afc187e574b8aa18d4fdbc77b32f0
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09334261B2

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