Ethyl Acrylate → Ethyl-3-[3-[[2-[3-(2,2-dimethylpropanoylamino)-4-methyl-phenyl]imidazo[2,1-f]pyridazin-6-yl]carbamoyl]phenyl]prop-2-enoate

HRID 539804Notes

Reaction equation

HRID 539804 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:31]=[CH:32][CH:33]=1)[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]2=[N:14][C:15]([C:17]3[CH:22]=[CH:21][C:20]([CH3:23])=[C:19]([NH:24][C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])[CH:18]=3)=[CH:16][N:10]2[N:9]=1)=[O:6].[C:34]([O:38][CH2:39][CH3:40])(=[O:37])[CH:35]=[CH2:36].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.CCN(C(C)C)C(C)C>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:39]([O:38][C:34](=[O:37])[CH:35]=[CH:36][C:2]1[CH:33]=[CH:32][CH:31]=[C:4]([C:5](=[O:6])[NH:7][C:8]2[CH:13]=[CH:12][C:11]3=[N:14][C:15]([C:17]4[CH:22]=[CH:21][C:20]([CH3:23])=[C:19]([NH:24][C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])[CH:18]=4)=[CH:16][N:10]3[N:9]=2)[CH:3]=1)[CH3:40]

Participants

7

Reactant 4

HCID 8821Ethyl AcrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 679831683-bromo-N-[2-[3-(2,2-dimethylpropanoylamino)-4-methyl-phenyl]imidazo[2,1-f]pyridazin-6-yl]benzamide

Product 1

HCID 67983260Ethyl-3-[3-[[2-[3-(2,2-dimethylpropanoylamino)-4-methyl-phenyl]imidazo[2,1-f]pyridazin-6-yl]carbamoyl]phenyl]prop-2-enoateYield 30.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture of 3-bromo-N-[2-[3-(2,2-dimethylpropanoylamino)-4-methyl-phenyl]imidazo[2,1-f]pyridazin-6-yl]benzamide (0.126 g, 0.25 mmol), Ethyl acrylate (0.272 mL, 2.5 mmol), palladium(II) acetate (2.8 mg, 0.01 mmol), tri(o-tolyl)phosphine (0.0152 g, 0.05 mmol) in DMF (1.45 mL) is added DIPEA (0.174 mL, 1 mmol). The mixture is degassed with N2 then sealed and heated at 110° C. for 18 hours. The reaction mixture is cooled, saturated aqueous NaHCO3 (50 mL) added and extracted with EtOAc (×3). Organic layers are combined and washed with water, NaHCO3, brine, then dried, concentrated and purified by silica gel chromatography (0-100% EtOAc in Hexanes) to give the title compound (0.040 g). LCMS (m/z)=526.6 [M+H]+, tR=2.92 min.

Workup

  1. customThe mixture is degassed with N2
  2. customthen sealed
  3. temperatureThe reaction mixture is cooled
  4. additionsaturated aqueous NaHCO3 (50 mL) added
  5. extractionextracted with EtOAc (×3)
  6. washwashed with water, NaHCO3, brine
  7. customdried
  8. concentrationconcentrated
  9. custompurified by silica gel chromatography (0-100% EtOAc in Hexanes)

Sources & evidence

ORD record
ord-5d3303aea8d649729c72ac8e8788c410
Source dataset
uspto-grants-2014_10
Patent number
US08871767B2

Reaction notes

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