1,4-Cyclohexadiene → HCID 24765038, compound

HRID 1665994Notes

Reaction equation

HRID 1665994 reaction equation
[P:1]([O:19][CH2:20][CH2:21][N:22]1[C:30]2[C:25](=[CH:26][C:27]([O:31][C:32]3[CH:37]=[CH:36][C:35]([F:38])=[CH:34][C:33]=3[CH2:39][NH:40][C:41]([NH:43][C:44]3[N:48]([C:49]4[CH:54]=[CH:53][C:52]([CH3:55])=[CH:51][CH:50]=4)[N:47]=[C:46]([C:56]([CH3:59])([CH3:58])[CH3:57])[CH:45]=3)=[O:42])=[CH:28][CH:29]=2)[CH:24]=[N:23]1)([O:11]CC1C=CC=CC=1)([O:3]CC1C=CC=CC=1)=[O:2].C1CC=CCC=1>CCO.CO.[Pd]>[P:1]([O:19][CH2:20][CH2:21][N:22]1[C:30]2[C:25](=[CH:26][C:27]([O:31][C:32]3[CH:37]=[CH:36][C:35]([F:38])=[CH:34][C:33]=3[CH2:39][NH:40][C:41]([NH:43][C:44]3[N:48]([C:49]4[CH:50]=[CH:51][C:52]([CH3:55])=[CH:53][CH:54]=4)[N:47]=[C:46]([C:56]([CH3:59])([CH3:58])[CH3:57])[CH:45]=3)=[O:42])=[CH:28][CH:29]=2)[CH:24]=[N:23]1)([OH:11])([OH:3])=[O:2]

Participants

6

Reactant 2

HCID 123431,4-CyclohexadieneHCID 57552298HCID 57552298, compound

Product 1

HCID 24765038HCID 24765038, compoundYield 89%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 887MethanolSolvent

Procedure

Dibenzyl 2-(5-(2-((3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido)methyl)-4-fluorophenoxy)-1H-indazol-1-yl)ethyl phosphate (1.920 g, 2.35 mmol) was suspended in EtOH (0.05M, 50 mL) and cyclohexa-1,4-diene (3.56 ml, 82.14 mmol) and 10% Pd/C (20%/weight, 0.384 g) were added. The reaction mixture was refluxed overnight. The reaction mixture was filtered through GF paper and washed with MeOH. The organic layers were concentrated under reduced pressure to afford the crude material, which was dissolved in MeOH and passed through a Gellman acrodisk (0.45 um) filter to remove trace of palladium contamination. After evaporation of the solvent, the resulting gum was triturated in CH3CN and solids formed were collected by filtration and dried under high vacuum for 3 hours to provide 1.21 g (89%) of the desired compound. MS (APCI+) m/z 637 (M+1) was detected. 1H NMR (400 MHz, DMSO-d6) δ 8.30 (s, 1H), 8.00 (s, 1H), 7.71 (d, 1H, J=9 Hz), 6.88-7.37 (m, 10H), 6.24 (s, 1H), 4.61 (br, 1H), 4.28 (d, 2H, J=5.7 Hz), 4.19 (dd, 2H, J=5.2 Hz), 2.35 (s, 3H), 1.25 (s, 9H).

Workup

  1. temperatureThe reaction mixture was refluxed overnight
  2. filtrationThe reaction mixture was filtered through GF paper
  3. washwashed with MeOH
  4. concentrationThe organic layers were concentrated under reduced pressure
  5. customto afford the crude material, which
  6. filtrationfilter
  7. customto remove trace of palladium contamination
  8. customAfter evaporation of the solvent
  9. customthe resulting gum was triturated in CH3CN
  10. customsolids formed
  11. filtrationwere collected by filtration
  12. customdried under high vacuum for 3 hours

Sources & evidence

ORD record
ord-bf0ff525ae2d42f094fa727708b34a72
Source dataset
uspto-grants-2011_10
Patent number
US08039639B2

Reaction notes

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