Methyl Acrylate → (E)-3-{2-[4-(1-tert-butoxycarbonylamino-cyclobutyl)-phenyl]-3-phenyl-imidazo[1,2-a]pyridin-7-yl}-acrylic acid methyl ester

HRID 872327Notes

Reaction equation

HRID 872327 reaction equation
[C:1]([O:5][C:6](=[O:34])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:19]=[C:20]4[CH:25]=[C:24](Br)[CH:23]=[CH:22][N:21]4[C:27]=3[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[C:35]([O:39][CH3:40])(=[O:38])[CH:36]=[CH2:37].C(N(CC)CC)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[NH4+].[Cl-]>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(Cl)Cl.O>[CH3:40][O:39][C:35](=[O:38])/[CH:36]=[CH:37]/[C:24]1[CH:23]=[CH:22][N:21]2[C:27]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[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:34])[CH2:11][CH2:10][CH2:9]4)=[CH:13][CH:14]=3)[N:19]=[C:20]2[CH:25]=1

Participants

10

Reactant 5

HCID 7294Methyl AcrylateHCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 80271Tri-o-tolylphosphineHCID 66665545{1-[4-(7-Bromo-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

Product 1

HCID 66665952(E)-3-{2-[4-(1-tert-butoxycarbonylamino-cyclobutyl)-phenyl]-3-phenyl-imidazo[1,2-a]pyridin-7-yl}-acrylic acid methyl esterYield 83.8%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
150 °C

Procedure

To a mixture of {1-[4-(7-bromo-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (534 mg, 1.03 mmol), methyl acrylate (0.19 mL, 2.06 mmol, 2.0 equiv), triethylamine (0.16 mL, 1.17 mmol, 1.1 equiv), palladium(II) acetate (17 mg, 0.08 mmol, 7 mol %) and tri (2-tolyl)phosphine (53 mg, 0.18 mmol, 17 mol %) in acetonitrile (7 mL) was heated at 150° C. for 2 h. in a microwave apparatus. The reaction mixture was mixed with water (10 mL), a saturated aqueous NH4Cl solution (10 mL) and CH2Cl2 (25 mL) with vigorous stirring at room temperature for 30 min. The resulting organic phase was washed with a saturated aqueous NaCl solution, dried (Na2SO4 anh), and concentrated under reduced pressure to give (E)-3-{2-[4-(1-tert-butoxycarbonylamino-cyclobutyl)-phenyl]-3-phenyl-imidazo[1,2-a]pyridin-7-yl}-acrylic acid methyl ester (452 mg, 75%):

Workup

  1. washThe resulting organic phase was washed with a saturated aqueous NaCl solution
  2. dry with materialdried (Na2SO4 anh)
  3. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-52c67ee53cb94a89b0226afb4b3a67aa
Source dataset
uspto-grants-2015_03
Patent number
US08975265B2

Reaction notes

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