Ethyl Acetate → 1-(4-Fluorophenyl)-4-oxo-6-(pyridin-3-yl)-1,4-dihydroquinoline-3-carboxamide

HRID 1048892Notes

Reaction equation

HRID 1048892 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)[CH:7]=[C:6]([C:19]([NH2:21])=[O:20])[C:5]2=[O:22].[N:23]1[CH:28]=[CH:27][CH:26]=[C:25](B(O)O)[CH:24]=1.C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C>C(COC)OC.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].O>[F:18][C:15]1[CH:16]=[CH:17][C:12]([N:8]2[C:9]3[C:4](=[CH:3][C:2]([C:25]4[CH:24]=[N:23][CH:28]=[CH:27][CH:26]=4)=[CH:11][CH:10]=3)[C:5](=[O:22])[C:6]([C:19]([NH2:21])=[O:20])=[CH:7]2)=[CH:13][CH:14]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 1214478716-Bromo-1-(4-fluorophenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide

Product 1

HCID 1214478831-(4-Fluorophenyl)-4-oxo-6-(pyridin-3-yl)-1,4-dihydroquinoline-3-carboxamideYield 68%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
150 °C

Procedure

Compound E (15 mg, 0.042 mmol, 1.0 eq), 3-pyridinylboronic acid (11 mg, 0.087 mmol, 2.1 eq), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (3.0 mg, 0.0042 mmol, 0.10 eq) and 1N sodium carbonate (0.21 mL, 0.21 mmol, 5.0 eq) were dissolved in dimethoxyethane (0.6 mL) in a microwave vial and heated at 150° C. for 20 minutes in a microwave reactor. The reaction was portioned between ethyl acetate and water and the layers separated. The aqueous phase was extracted with an additional portion of ethyl acetate and the combined organics were dried (MgSO4), filtered and concentrated in vacuo. Purification by reverse phase chromatography afforded 10.1 mg (68%) of the title compound as white solid. 1H NMR (400 MHz, DMSO-d6) δ 9.21 (d, J=4.3 Hz, 1H), 8.96 (d, J=1.9 Hz, 1H), 8.62 (m, 2H), 8.60 (s, 1H), 8.17 (dt, J=8.0, 1.7 Hz, 1H), 8.09 (dd, J=8.8, 2.3 Hz, 1H), 7.81-7.78 (m, 2H), 7.66 (d, J=4.3 Hz, 1H), 7.57-7.52 (m, 3H), 7.16 (d, J=8.8 Hz, 1H); ES-MS [M+1]+: 360.2.

Workup

  1. customthe layers separated
  2. extractionThe aqueous phase was extracted with an additional portion of ethyl acetate
  3. dry with materialthe combined organics were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by reverse phase chromatography

Sources & evidence

ORD record
ord-512fbfa1523d4d53a6b882d18c0eafd1
Source dataset
uspto-grants-2016_07
Patent number
US09382208B1

Reaction notes

Loading…