Dimethylformamide → 3-ethyl-2-(1-ethylpropyl)-6-{1-[4-(methylsulfonyl)phenyl]-1H-pyrazol-5-yl}-2H-indazole

HRID 2113714Notes

Reaction equation

HRID 2113714 reaction equation
[CH2:1]([C:3]1[C:11]2[C:6](=[CH:7][C:8]([C:12]3[N:16]([C:17]4[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][CH:18]=4)[N:15]=[CH:14][CH:13]=3)=[CH:9][CH:10]=2)[NH:5][N:4]=1)[CH3:2].Br[CH:28]([CH2:31][CH3:32])[CH2:29][CH3:30].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>C(OCC)(=O)C.O>[CH2:1]([C:3]1[N:4]([CH:28]([CH2:31][CH3:32])[CH2:29][CH3:30])[N:5]=[C:6]2[C:11]=1[CH:10]=[CH:9][C:8]([C:12]1[N:16]([C:17]3[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][CH:18]=3)[N:15]=[CH:14][CH:13]=1)=[CH:7]2)[CH3:2]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 157383-Bromopentane2×HCID 178437987HCID 178437987, compound

Product 1

HCID 598108023-ethyl-2-(1-ethylpropyl)-6-{1-[4-(methylsulfonyl)phenyl]-1H-pyrazol-5-yl}-2H-indazoleYield 3.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

3-ethyl-6-{1-[4-(methylsulfonyl)phenyl]-1H-pyrazol-5-yl}-1H-indazole (100 mg, 0.27 mmol), 3-bromopentane (70 mg, 0.46 mmol), potassium carbonate (45 mg, 0.33 mmol) and N,N-dimethylformamide (2 mL) were added to a 1-necked flask. The mixture was heated to 60° C. for 6 hours, then slowly cooled to room temperature and stirred for a further 48 hours. A further equivalent of 3-bromopentane (41 mg, 0.27 mmol) was then added, and the reaction was heated to 120° C. After cooling to room temperature, water and ethyl acetate were added. The product was extracted once with ethyl acetate, and washed with water and brine. The combined organics were dried, and filtered and concentrated. The reside was purified by column chromatography on silica gel (eluting using 50% ethyl acetate in hexanes for 10 minutes and then a linear gradient to 100% ethyl acetate in hexanes at 20 minutes) to give 4.4 mg (3.7%) of 3-ethyl-2-(1-ethylpropyl)-6-{1-[4-(methylsulfonyl)phenyl]-1H-pyrazol-5-yl}-2H-indazole. LC/MS (EI) tR 4.36 (Method C), m/z 437.1 (M++1), 1H NMR (CDCl3) δ 0.6 (t, 3H), 1.4 (t, 2H), 1.8 (m, 2H), 1.9 (m, 2H), 3.0 (m, 6H), 4.0 (m, 1H), 6.5 (s, 1H), 7.0 (d, 1H), 7.1 (s, 1H), 7.5 (d, 2H), 7.7 (m, 1H), 7.8 (s, 1H), 7.8 (d, 2H). 13 mg (11%) of the corresponding isomer (3-ethyl-1-(1-ethylpropyl)-6-{1-[4-(methylsulfonyl)phenyl]-1H-pyrazol-5-yl}-1H-indazole) was also isolated.

Workup

  1. temperatureslowly cooled to room temperature
  2. temperaturethe reaction was heated to 120° C
  3. temperatureAfter cooling to room temperature
  4. extractionThe product was extracted once with ethyl acetate
  5. washwashed with water and brine
  6. customThe combined organics were dried
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe reside was purified by column chromatography on silica gel (
  10. washeluting
  11. customfor 10 minutes

Sources & evidence

ORD record
ord-5b843bb5bd7a4cf089b552829c506231
Source dataset
uspto-grants-2008_10
Patent number
US07432266B2

Reaction notes

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