N,N'-Dimethylethylenediamine → 6-chloro-2-cyclopropyl-1-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-1H-indole

HRID 522777

반응식

HRID 522777 반응식
[Cl:1][C:2]1[C:10]([F:11])=[C:9]2[C:5]([CH:6]=[C:7]([CH:12]3[CH2:14][CH2:13]3)[NH:8]2)=[CH:4][CH:3]=1.Br[C:16]1[CH:17]=[N:18][N:19]([CH2:21][CH3:22])[CH:20]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CNCCNC>C1(C)C=CC=CC=1.CCOC(C)=O>[Cl:1][C:2]1[C:10]([F:11])=[C:9]2[C:5]([CH:6]=[C:7]([CH:12]3[CH2:14][CH2:13]3)[N:8]2[C:16]2[CH:17]=[N:18][N:19]([CH2:21][CH3:22])[CH:20]=2)=[CH:4][CH:3]=1

참가 물질

7

반응물 4

HCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 125652014-Bromo-1-ethyl-1H-pyrazoleHCID 1179791976-chloro-2-cyclopropyl-7-fluoro-1H-indole

생성물 1

HCID 1181041966-chloro-2-cyclopropyl-1-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-1H-indole수율 63%

시약·촉매·용매 2

HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

반응 조건

온도
140 °C

실험 절차

To a solution of compound 3 (4.3 g, 20.5 mmol) in toluene (50 mL) were added 4-bromo-1-ethyl-1H-pyrazole 4 (Example 2, Step 3; 4.0 g, 22.8 mmol), potassium phosphate (11.0 g, 51.2 mmol), N,N′-dimethylethylenediamine (722 mg, 8.2 mmol) and Cu(I)I (390 mg, 2.0 mmol) at RT under inert atmosphere. The reaction solution was purged with argon for 15 min and then sealed the tube. The reaction mixture was heated to 140° C. and stirred for 16 h. After completion of the reaction (TLC), the reaction mixture was cooled to RT, diluted with EtOAc (50 mL) and filtered. The filtrate was washed with water (40 mL), brine (40 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude. The crude was purified (silica gel column chromatography; 9% EtOAc/Hexanes) to afford compound 5 (3.9 g, 63%) as a pale brown solid. 1H NMR (400 MHz, CDCl3): δ 7.64 (s, 1H), 7.60 (s, 1H), 7.16 (d, J=8.4 Hz, 1H), 7.01 (dd, J=8.4, 6.4 Hz, 1H), 6.12 (s, 1H), 4.25 (q, J=7.2 Hz, 2H), 1.69-1.62 (m, 1H), 1.56 (t, J=7.2 Hz, 3H), 0.92-0.87 (m, 2H), 0.76-0.72 (m, 2H); LC-MS (ESI): 98.6%; m/z 304.3 (M+H+); (column: X Select C-18, 50×3.0 mm, 3.5 μm); RT 4.23 min; 5 mM NH4OAc: ACN; 0.8 mL/min).

후처리

  1. customThe reaction solution was purged with argon for 15 min
  2. customsealed the tube
  3. customAfter completion of the reaction (TLC)
  4. temperaturethe reaction mixture was cooled to RT
  5. filtrationfiltered
  6. washThe filtrate was washed with water (40 mL), brine (40 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 column chromatography; 9% EtOAc/Hexanes)

출처 및 근거

ORD 기록
ord-e3c73dbbb9f34f8cba440563e77ca8e6
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09334261B2

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