HCID 66773299, compound → HCID 178509480, compound

HRID 1256251Notes

Reaction equation

HRID 1256251 reaction equation
Br[C:2]1[C:6]2[N:7]=[C:8](C3C(F)=CC=CC=3F)[C:9]3[CH:10]=[C:11]([C:15]#[N:16])[CH:12]=[CH:13][C:14]=3[C:5]=2[N:4](COCC[Si](C)(C)C)[N:3]=1>O1CCOCC1>[N:4]1[NH:3][CH:2]=[C:6]2[C:5]=1[C:14]1[CH:13]=[CH:12][C:11]([C:15]#[N:16])=[CH:10][C:9]=1[CH:8]=[N:7]2

Participants

3

Reactant 1

HCID 66773299HCID 66773299, compound

Product 1

HCID 178509480HCID 178509480, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

707 mg of 3-bromo-5-(2,6-difluorophenyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[4,3-c]isoquinoline-7-carbonitrile are introduced into 17 ml of 1,4-dioxane. After argon has been bubbled through the mixture for 10 min, 846 mg of 4-aminopiperidine-1-sulphonamide, 2.15 g of caesium carbonate, 95 mg of 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene and 30 mg of palladium(II) acetate are added. The mixture is heated at reflux for 20 h. After cooling, the mixture is poured into water, extracted with AcOEt, washed with saturated NaCl solution, dried over MgSO4, filtered and concentrated under RP. The product is purified by flash chromatography on silica gel (40-63 μm), eluting with a DCM/EtOH/NH3 (7N solution in MeOH) mixture (90/10/1 by vol.), to give 407 mg of 5-(2,6-difluorophenyl)-3-(piperidin-4-ylamino)-2-[2-(trimethylsilyl)ethoxy]methyl}-2H-pyrazolo[4,3-c]isoquinoline-7-carbonitrile (yellow oil). 1H NMR: −0.05 (broad s, 9 H) 0.88 (t, J=7.9 Hz, 2 H) 1.39 (m, 2 H) 1.93 (m, 2 H) 2.08 (broad m, 1 H) 2.39 (m, 2 H) 2.93 (m, 2 H) 3.71 (t, J=7.9 Hz, 2 H) 4.42 (m, 1H) 5.66 (s, 2 H) 6.58 (d, J=8.1 Hz, 1 H) 7.33 (t, J=7.9 Hz, 2 H) 7.66 (m, 1 H) 7.95 (broad s, 1 H) 8.12 (broad d, J=8.3 Hz, 1 H) 8.46 (d, J=8.3 Hz, 1 H).

Workup

  1. customAfter argon has been bubbled through the mixture for 10 min
  2. addition846 mg of 4-aminopiperidine-1-sulphonamide, 2.15 g of caesium carbonate, 95 mg of 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene and 30 mg of palladium(II) acetate are added
  3. temperatureThe mixture is heated
  4. temperatureat reflux for 20 h
  5. temperatureAfter cooling
  6. additionthe mixture is poured into water
  7. extractionextracted with AcOEt
  8. washwashed with saturated NaCl solution
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated under RP
  12. customThe product is purified by flash chromatography on silica gel (40-63 μm)
  13. washeluting with a DCM/EtOH/NH3 (7N solution in MeOH) mixture (90/10/1 by vol.)

Sources & evidence

ORD record
ord-ff5d31a60b6c43b99c66248fdac79977
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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