Acrylamide → HCID 68082225, compound

HRID 872328Notes

Reaction equation

HRID 872328 reaction equation
[C:1]([O:5][C:6](=[O:35])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:19]=[C:20]4[C:25](Br)=[CH:24][C:23]([CH3:27])=[CH:22][N:21]4[C:28]=3[C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[C:36]([NH2:40])(=[O:39])[CH:37]=[CH2:38].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(#N)C>[C:1]([O:5][C:6](=[O:35])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:19]=[C:20]4[C:25](/[CH:38]=[CH:37]/[C:36](=[O:39])[NH2:40])=[CH:24][C:23]([CH3:27])=[CH:22][N:21]4[C:28]=3[C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 6579Acrylamide2×HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 66665285HCID 66665285, compound

Product 1

HCID 68082225HCID 68082225, compoundYield 51.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalyst2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
110 °C

Procedure

50 mg (0.09 mmol) {1-[4-(8-Bromo-6-methyl-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester, 13.4 mg (0.19 mmol) acryl amide, 4.86 mg (0.016 mmol) tri-2-tolylphosphane, 2.1 mg (0.009 mmol) palladium(II) acetate and 0.02 mL (0.1 mmol) triethylamine in 0.7 mL degassed acetonitrile were heated in the microwave at 110° C. for 60′. Due to an incomplete reaction additional 13.3 mg acrylamide and 4.2 mg palladium(II) acetate were added, and heating in the microwave was continued for two hours. The reaction mixture was poured on water/saturated ammonium chloride/dichloromethane and vigorously stirred for 30 minutes. The organic phase was separated and the aqueous phase was once more extracted with dichloromethane. The combined organic extracts were washed twice with brine, dried, and the solvent was removed. The crude product (76 mg) was purified by chromatography on silicagel (eluents: hexane/ethyl acetate) yielding 24.2 mg (49.3%) of the desired compound.

Workup

  1. temperatureheating in the microwave
  2. additionThe reaction mixture was poured on water/saturated ammonium chloride/dichloromethane
  3. customThe organic phase was separated
  4. extractionthe aqueous phase was once more extracted with dichloromethane
  5. washThe combined organic extracts were washed twice with brine
  6. customdried
  7. customthe solvent was removed
  8. customThe crude product (76 mg) was purified by chromatography on silicagel (eluents: hexane/ethyl acetate)

Sources & evidence

ORD record
ord-69fb77f07ef2457b89f5fe0b5c6b5737
Source dataset
uspto-grants-2015_03
Patent number
US08975265B2

Reaction notes

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