Potassium Carbonate → (S)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-5-((1-(prop-1-en-1-yl)-1H-benzo[d]imidazol-2-yl)oxy)-1,2,3,4-tetrahydroquinoline

HRID 1051731Notes

Reaction equation

HRID 1051731 reaction equation
[CH2:1]([N:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]=[C:5]1[O:13][C:14]1[C:23](Br)=[CH:22][CH:21]=[C:20]2[C:15]=1[CH2:16][CH2:17][C@H:18]([CH3:25])[NH:19]2)[CH:2]=[CH2:3].[CH:26]1([N:29]2[CH:33]=[C:32](B3OC(C)(C)C(C)(C)O3)[CH:31]=[N:30]2)[CH2:28][CH2:27]1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl>[CH:26]1([N:29]2[CH:33]=[C:32]([C:23]3[C:14]([O:13][C:5]4[N:4]([CH:1]=[CH:2][CH3:3])[C:8]5[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=5[N:6]=4)=[C:15]4[C:20](=[CH:21][CH:22]=3)[NH:19][C@@H:18]([CH3:25])[CH2:17][CH2:16]4)[CH:31]=[N:30]2)[CH2:28][CH2:27]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 593271331-Cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 118076020(S)-5-(1-allyl-1H-benzo[d]imidazol-2-yloxy)-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline

Product 1

HCID 131736102(S)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-5-((1-(prop-1-en-1-yl)-1H-benzo[d]imidazol-2-yl)oxy)-1,2,3,4-tetrahydroquinolineYield 86%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (S)-5-(1-allyl-1H-benzo[d]imidazol-2-yloxy)-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline (0.115 g, 0.29 mmol), 1-cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.269 g, 1.15 mmol), potassium carbonate (0.118 g, 0.85 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (0.023 g, 0.03 mmol) in 1,4-dioxane (10 mL) and water (3 mL) stirred for 3 h at 100° C. The reaction mixture was cooled to room temperature, filtered through a short pad of Celite and concentrated under vacuum. The residue was purified via preparative thin layer chromatography (eluting with 1:2, ethyl acetate/petroleum ether) to afford (S)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-5-((1-(prop-1-en-1-yl)-1H-benzo[d]imidazol-2-yl)oxy)-1,2,3,4-tetrahydroquinoline (0.106 g, 86%) as a red oil which is mixture of E and Z isomers. MS (ESI, pos. ion) m/z 426 [M+H]+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered through a short pad of Celite
  3. concentrationconcentrated under vacuum
  4. customThe residue was purified via preparative thin layer chromatography (eluting with 1:2, ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-320891dabf6e4ca5836a2a078e03a501
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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