Ethyl Acetate → 2-(2-Fluorophenyl)-3-methyl-N-(2-(4-morpholinyl)-5-(3-thiophenyl)phenyl)-4-quinolinamine

HRID 1431296Notes

Reaction equation

HRID 1431296 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)=[C:6]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]=[C:11]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[F:25])[C:10]=2[CH3:26])[CH:7]=1.[S:33]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34]1.C(=O)([O-])[O-].[Na+].[Na+].CCOC(C)=O>O.O1CCOCC1.CCCCCC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:25][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=1[C:11]1[C:10]([CH3:26])=[C:9]([NH:8][C:6]2[CH:7]=[C:2]([C:35]3[CH:36]=[CH:37][S:33][CH:34]=3)[CH:3]=[CH:4][C:5]=2[N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:12]=1

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 581760Thiophene-3-boronic acidHCID 59631162N-(5-Bromo-2-morpholinophenyl)-2-(2-fluorophenyl)-3-methylquinolin-4-amine

Product 1

HCID 509061372-(2-Fluorophenyl)-3-methyl-N-(2-(4-morpholinyl)-5-(3-thiophenyl)phenyl)-4-quinolinamine

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 8058HexaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of dichlorobis(triphenylphosphine)palladium(II) (13 mg, 18 μmol), N-(5-bromo-2-morpholinophenyl)-2-(2-fluorophenyl)-3-methylquinolin-4-amine (88 mg, 179 μmol), thiophen-3-ylboronic acid (34 mg, 268 μmol) and sodium carbonate (57 mg, 536 μmol) in water (0.25 mL) and 1,4-dioxane (1.00 mL) was purged with nitrogen then heated in a microwave vessel to 130° C. for 60 min, after which time TLC indicated no starting material remained and LC-MS indicated only desired product present. The reaction was partitioned between water and EtOAc (30 mL ea). The organic separation was stirred over anhydrous magnesium sulfate, filtered and the filtrate concentrated under reduced pressure to afford a brown film. The desired product was isolated by chromatography on silica gel eluting isocratically with 33% EtOAc in hexane to afford a colorless solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.99 (2H, dd, J=15.3, 8.2 Hz), 7.79 (1H, s), 7.71 (1H, dd, J=7.0, 7.0 Hz), 7.45-7.63 (5H, m), 7.32-7.45 (2H, m), 7.12-7.29 (3H, m), 6.69 (1H, d, J=1.6 Hz), 3.59 (4H, br. s.), 2.91 (4H, br. s.), 2.06 (3H, d, J=1.6 Hz). Mass Spectrum (ESI) m/e=496.1 (M+1).

Workup

  1. customwas purged with nitrogen
  2. customThe reaction was partitioned between water and EtOAc (30 mL ea)
  3. customThe organic separation
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated under reduced pressure
  6. customto afford a brown film

Sources & evidence

ORD record
ord-c84a2ad9e7144fe8a957f093a38c2bd1
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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