Potassium Carbonate → N-(3-((7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)amino)-5-(4-morpholinyl)phenyl)-2-methylpropanamide

HRID 1431786Notes

Reaction equation

HRID 1431786 reaction equation
CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.Cl[C:36]1[C:45]2[C:40](=[CH:41][C:42]([F:46])=[CH:43][CH:44]=2)[N:39]=[C:38]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][N:48]=2)[C:37]=1[CH3:53].[NH2:54][C:55]1[CH:56]=[C:57]([NH:67][C:68](=[O:72])[CH:69]([CH3:71])[CH3:70])[CH:58]=[C:59]([N:61]2[CH2:66][CH2:65][O:64][CH2:63][CH2:62]2)[CH:60]=1.C(=O)([O-])[O-].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(O)(C)(C)C>[F:46][C:42]1[CH:41]=[C:40]2[C:45]([C:36]([NH:54][C:55]3[CH:56]=[C:57]([NH:67][C:68](=[O:72])[CH:69]([CH3:70])[CH3:71])[CH:58]=[C:59]([N:61]4[CH2:66][CH2:65][O:64][CH2:63][CH2:62]4)[CH:60]=3)=[C:37]([CH3:53])[C:38]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][N:48]=3)=[N:39]2)=[CH:44][CH:43]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596310754-Chloro-7-fluoro-3-methyl-2-(pyridin-2-yl)quinolineHCID 67507609N-(3-amino-5-morpholinophenyl)isobutyramide

Product 1

HCID 59631591N-(3-((7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)amino)-5-(4-morpholinyl)phenyl)-2-methylpropanamide

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6386tert-ButanolSolvent

Procedure

Prepared according to Procedure X by stirring palladium (II) acetate (2.325 mg, 10.36 μmol), XPhos (0.015 g, 0.031 mmol), 4-chloro-7-fluoro-3-methyl-2-(pyridin-2-yl)quinoline (0.056 g, 0.207 mmol), N-(3-amino-5-morpholinophenyl)-isobutyramide (0.060 g, 0.228 mmol), potassium carbonate (0.072 g, 0.518 mmol), and tert-butanol (1 mL) at 110° C. for 20 minutes. Purification by reverse-phase HPLC (0-70% acetonitrile in water) afforded N-(3-((7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)amino)-5-(4-morpholinyl)phenyl)-2-methylpropanamide as a yellow amorphous solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.74 (1H, d, J=4.5 Hz), 7.92 (2H, d, J=6.8 Hz), 7.86 (1H, s), 7.78 (1H, d), 7.42 (1H, t), 7.18 (2H, m), 6.35 (1H, br. s.), 6.11 (1H, s), 3.74-3.84 (4H, m), 3.05-3.17 (4H, m), 2.32 (3H, s), 1.20 (3H, s), 1.18 (3H, s). Mass Spectrum (ESI) m/e=499.8 (M+1).

Workup

  1. customPrepared
  2. customPurification by reverse-phase HPLC (0-70% acetonitrile in water)

Sources & evidence

ORD record
ord-6b6e2084feb04b218b1542147ba9c65e
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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