Cesium carbonate → Ethyl 2-(4-((2-(3-hydroxycyclopent-1-en-1-yl)-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)amino)phenyl)acetate

HRID 1508802Notes

Reaction equation

HRID 1508802 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH2:12][CH2:11][CH:10]([OH:13])[CH:9]=2)[N:5]=[C:4]2[CH2:14][CH2:15][CH2:16][C:3]=12.[CH2:17]([O:19][C:20](=[O:29])[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([NH2:28])=[CH:24][CH:23]=1)[CH3:18].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(OCC)(=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH4+:5].[OH-:13].[OH:13][CH:10]1[CH2:11][CH2:12][C:8]([C:6]2[N:5]=[C:4]3[CH2:14][CH2:15][CH2:16][C:3]3=[C:2]([NH:28][C:25]3[CH:24]=[CH:23][C:22]([CH2:21][C:20]([O:19][CH2:17][CH3:18])=[O:29])=[CH:27][CH:26]=3)[CH:7]=2)=[CH:9]1

Participants

10

Reactant 4

HCID 10796Cesium carbonateHCID 225219p-Aminophenylacetic acid ethyl esterHCID 634876Binap, (A+-)-HCID 903386203-(4-chloro-6,7-dihydro-5H-cyclopenta[b]pyridin-2-yl)cyclopent-2-enol

Product 2

HCID 14923Ammonium HydroxideHCID 90111095Ethyl 2-(4-((2-(3-hydroxycyclopent-1-en-1-yl)-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)amino)phenyl)acetateYield 112.9%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A 10-mL vial was charged with 3-(4-chloro-6,7-dihydro-5H-cyclopenta[b]pyridin-2-yl)cyclopent-2-enol (0.120 g, 0.51 mmol), 4-aminophenylacetic acid ethyl ester (0.096 g, 0.53 mmol), palladium acetate (0.006 g, 0.025 mmol), rac-BINAP (0.024 g, 0.038 mmol) and cesium carbonate (0.414 g, 1.27 mmol) in dioxane (6 mL) under argon. The reaction mixture was heated to 120° C. under microwave irradiation for 2 h. The reaction mixture was cooled, and diluted with ethyl acetate (75 mL) and water (5 mL). The organic layer was washed with saturated sodium chloride (2×5 mL), dried over sodium sulfate, filtered, and the filtrate concentrated under reduced pressure. The residue was purified by chromatography on silica using 80:20:1 dichloromethane/methanol/conc. NH4OH as the eluent to afford the title compound (0.109 g, 56%) as an oil. MW=378.46. 1H NMR (CDCl3, 500 MHz) δ 7.28 (d, J=8.0 Hz, 2H), 7.14 (d, J=8.0 Hz, 2H), 6.93 (s, 1H), 6.50 (d, J=1.5 Hz, 1H), 5.83 (s, 1H), 5.00-4.94 (m, 1H), 4.18 (q, J=7.0 Hz, 2H), 3.61 (s, 2H), 3.03 (t, J=7.5 Hz, 2H), 2.90-2.82 (m, 1H), 2.79 (t, J=7.5 Hz, 2H), 2.66-2.58 (m, 1H), 2.46-2.37 (m, 1H), 2.20-2.11 (m, 3H), 1.87-1.80 (m, 1H), 1.28 (t, J=7.0 Hz, 3H). ESI m/z 379 [M+H]+.

Workup

  1. temperatureThe reaction mixture was cooled
  2. washThe organic layer was washed with saturated sodium chloride (2×5 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated under reduced pressure
  6. customThe residue was purified by chromatography on silica using 80:20:1 dichloromethane/methanol/conc

Sources & evidence

ORD record
ord-f75a6d72d6c94c299649ec60cf20e2f3
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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