Ethyl Acrylate → Ethyl-3-[3-[[2-methyl-5-[6-[2-(trifluoromethyl)-3-pyridyl]imidazo[2,1-f]pyridazin-2-yl]phenyl]carbamoyl]phenyl]prop-2-enoate

HRID 539810Notes

Reaction equation

HRID 539810 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:34]=[CH:35][CH:36]=1)[C:5]([NH:7][C:8]1[CH:13]=[C:12]([C:14]2[N:15]=[C:16]3[N:21]([CH:22]=2)[N:20]=[C:19]([C:23]2[C:24]([C:29]([F:32])([F:31])[F:30])=[N:25][CH:26]=[CH:27][CH:28]=2)[CH:18]=[CH:17]3)[CH:11]=[CH:10][C:9]=1[CH3:33])=[O:6].[C:37]([O:41][CH2:42][CH3:43])(=[O:40])[CH:38]=[CH2:39].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.CN(P(N(C)C)(N(C)C)=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:42]([O:41][C:37](=[O:40])[CH:38]=[CH:39][C:2]1[CH:36]=[CH:35][CH:34]=[C:4]([C:5](=[O:6])[NH:7][C:8]2[CH:13]=[C:12]([C:14]3[N:15]=[C:16]4[N:21]([CH:22]=3)[N:20]=[C:19]([C:23]3[C:24]([C:29]([F:32])([F:31])[F:30])=[N:25][CH:26]=[CH:27][CH:28]=3)[CH:18]=[CH:17]4)[CH:11]=[CH:10][C:9]=2[CH3:33])[CH:3]=1)[CH3:43]

Participants

8

Reactant 4

HCID 8821Ethyl AcrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 680892223-bromo-N-[2-methyl-5-[6-[2-(trifluoromethyl)-3-pyridyl]imidazo[2,1-f]pyridazin-2-yl]phenyl]benzamide

Product 1

HCID 68089126Ethyl-3-[3-[[2-methyl-5-[6-[2-(trifluoromethyl)-3-pyridyl]imidazo[2,1-f]pyridazin-2-yl]phenyl]carbamoyl]phenyl]prop-2-enoateYield 106.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 3-bromo-N-[2-methyl-5-[6-[2-(trifluoromethyl)-3-pyridyl]imidazo[2,1-f]pyridazin-2-yl]phenyl]benzamide (0.442 g, 0.8 mmol), ethyl acrylate (0.872 mL, 8 mmol), palladium(II) acetate (9 mg, 0.04 mmol), tri(o-tolyl)phosphine (0.049 g, 0.16 mmol) in DMF (4.6 mL) and HMPA (0.4 mL) is added DIPEA (0.557 mL, 3.2 mmol). The mixture is degassed with N2 then sealed and heated at 100° C. for 15 hours. The reaction is not complete, and is stirred at 100° C. for another 24 hours. The mixture is poured into saturated aqueous NaHCO3 and extracted with EtOAc (2×). Organic layers are combined, dried and concentrated to give the title compound as a solid (485 mg), which is used without further purification. LCMS (m/z)=572.5 [M+H]+, tR=3.14 min.

Workup

  1. customThe mixture is degassed with N2
  2. customthen sealed
  3. additionThe mixture is poured into saturated aqueous NaHCO3
  4. extractionextracted with EtOAc (2×)
  5. customdried
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-bec0657857f342688e8f88cae912ce90
Source dataset
uspto-grants-2014_10
Patent number
US08871767B2

Reaction notes

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