Methanol → 2-(2-Fluorophenyl)-3-methyl-N-(2-(4-morpholinyl)-5-(4-pyridinyl)phenyl)-4-quinolinamine

HRID 1431295Notes

Reaction equation

HRID 1431295 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[N:7]1[CH:12]=[CH:11][C:10](B(O)O)=[CH:9][CH:8]=1.Br[C:17]1[CH:18]=[CH:19][C:20]([N:42]2[CH2:47][CH2:46][O:45][CH2:44][CH2:43]2)=[C:21]([NH:23][C:24]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[N:27]=[C:26]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[F:40])[C:25]=2[CH3:41])[CH:22]=1.CO>O.O1CCOCC1.C(Cl)Cl.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:40][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=1[C:26]1[C:25]([CH3:41])=[C:24]([NH:23][C:21]2[CH:22]=[C:17]([C:10]3[CH:11]=[CH:12][N:7]=[CH:8][CH:9]=3)[CH:18]=[CH:19][C:20]=2[N:42]2[CH2:47][CH2:46][O:45][CH2:44][CH2:43]2)[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[N:27]=1

Participants

9

Reactant 4

HCID 887MethanolHCID 10340Sodium CarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 59631162N-(5-Bromo-2-morpholinophenyl)-2-(2-fluorophenyl)-3-methylquinolin-4-amine

Product 1

HCID 596315472-(2-Fluorophenyl)-3-methyl-N-(2-(4-morpholinyl)-5-(4-pyridinyl)phenyl)-4-quinolinamine

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of sodium carbonate (68 mg, 640 μmol), pyridin-4-ylboronic acid (40 mg, 329 μmol), N-(5-bromo-2-morpholinophenyl)-2-(2-fluorophenyl)-3-methylquinolin-4-amine (90 mg, 183 μmol) and dichlorobis(triphenylphosphine)-palladium(II) (13 mg, 18 μmol) in water (2.00 mL) and 1,4-dioxane (8.00 mL) was purged with nitrogen then heated in a microwave vessel with stirring at 130° C. for 60 min, after which time LC-MS indicated no starting material remained and desired product predominated. The reaction was diluted with 30 mL water and extracted with 3×15 mL EtOAc. The combined organic extracts were stirred over magnesium sulfate, filtered and the filtrate concentrated under reduced pressure to afford a dark brown oil. The desired product was isolated as a colorless solid by chromatography on silica gel eluting with a gradient of 1-5% MeOH in DCM. 1H NMR (400 MHz, chloroform-d) δ ppm 8.55 (2H, dd, J=4.3, 1.6 Hz), 8.21 (1H, d, J=8.2 Hz), 7.93 (1H, d, J=8.6 Hz), 7.61-7.79 (3H, m), 7.40-7.61 (3H, m), 7.10-7.40 (7H, m), 6.74 (1H, d, J=0.8 Hz), 3.98 (4H, t, J=4.5 Hz), 3.02-3.29 (4H, m), 2.26 (3H, d, J=2.3 Hz). Mass Spectrum (ESI) m/e=491.2 (M+1).

Workup

  1. customwas purged with nitrogen
  2. temperaturethen heated in a microwave vessel
  3. additionThe reaction was diluted with 30 mL water
  4. extractionextracted with 3×15 mL EtOAc
  5. stirringThe combined organic extracts were stirred over magnesium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated under reduced pressure
  8. customto afford a dark brown oil

Sources & evidence

ORD record
ord-36b7f39d7149443cbaaa6fc2822b49f8
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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