Methyl Acrylate → HCID 86692122, compound

HRID 876883Notes

Reaction equation

HRID 876883 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[C:19]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[CH:20][C:21]4[N:22]([C:24](Br)=[C:25]([CH3:27])[N:26]=4)[N:23]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[C:36]([O:40][CH3:41])(=[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>[CH3:41][O:40][C:36](=[O:39])/[CH:37]=[CH:38]/[C:24]1[N:22]2[N:23]=[C:18]([C:15]3[CH:16]=[CH:17][C:12]([C:8]4([NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:35])[CH2:11][CH2:10][CH2:9]4)=[CH:13][CH:14]=3)[C:19]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[CH:20][C:21]2=[N:26][C:25]=1[CH3:27]

Participants

7

Reactant 4

HCID 7294Methyl Acrylate2×HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 66714364HCID 66714364, compound

Product 1

HCID 86692122HCID 86692122, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalyst2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
110 °C

Procedure

200 mg (0.375 mmol) {1-[4-(3-Bromo-2-methyl-7-phenyl-imidazo[1,2-b]pyridazin-6-yl)-phenyl]-cyclobutyl}-carbamic acid tert.-butyl ester, intermediate example Int-2-3, 64.5 mg (0.75 mmol) methyl acrylate, 19.4 mg (0.064 mmol) tri-2-tolylphosphane, 16.8 mg (0.075 mmol) palladium(II) acetate and 0.06 mL (0.427 mmol) triethylamine in 2.6 mL degassed acetonitrile were heated in the microwave at 110° C. for three hours. Due to an incomplete reaction additional 32.2 mg (0.375 mmol) methyl acrylate and 8.5 mg (0.037 mmol) palladium(II) acetate were added, and heating in the microwave was continued for three hours. The reaction mixture was poured on water/saturated ammonium chloride/dichloromethane and vigorously stirred for 30 minutes. The organic phase was separated, washed twice with brine, dried, and the solvent was removed. The crude product (300 mg) was used in the next step without further purification.

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. washwashed twice with brine
  5. customdried
  6. customthe solvent was removed
  7. customThe crude product (300 mg) was used in the next step without further purification

Sources & evidence

ORD record
ord-5baee46c21304fe089d7b96adcfd7f63
Source dataset
uspto-grants-2015_03
Patent number
US08987273B2

Reaction notes

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