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

HRID 1431789Notes

Reaction equation

HRID 1431789 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:48]=[N:49][CH:50]=[C:51]([F:53])[CH:52]=2)[C:37]=1[CH3:54].[NH2:55][C:56]1[CH:57]=[C:58]([NH:68][C:69](=[O:71])[CH3:70])[CH:59]=[C:60]([N:62]2[CH2:67][CH2:66][O:65][CH2:64][CH2:63]2)[CH:61]=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:55][C:56]3[CH:57]=[C:58]([NH:68][C:69](=[O:71])[CH3:70])[CH:59]=[C:60]([N:62]4[CH2:67][CH2:66][O:65][CH2:64][CH2:63]4)[CH:61]=3)=[C:37]([CH3:54])[C:38]([C:47]3[CH:48]=[N:49][CH:50]=[C:51]([F:53])[CH:52]=3)=[N:39]2)=[CH:44][CH:43]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596314314-Chloro-7-fluoro-2-(5-fluoropyridin-3-yl)-3-methylquinolineHCID 67507700N-(3-amino-5-morpholinophenyl)acetamide

Product 1

HCID 59631543N-(3-((7-fluoro-2-(5-fluoro-3-pyridinyl)-3-methyl-4-quinolinyl)amino)-5-(4-morpholinyl)phenyl)acetamide

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6386tert-ButanolSolvent

Procedure

Prepared according to Procedure X by stirring palladium (II) acetate (1.545 mg, 6.88 μmol), XPhos (9.84 mg, 0.021 mmol), 4-chloro-7-fluoro-2-(5-fluoropyridin-3-yl)-3-methylquinoline (0.040 g, 0.138 mmol), N-(3-amino-5-morpholinophenyl)acetamide (0.032 g, 0.138 mmol), potassium carbonate (0.048 g, 0.344 mmol), and tert-butanol (1 mL) at 110° C. for 20 minutes. Purification by column chromatography (silica; 0-4% methanol in DCM) afforded N-(3-((7-fluoro-2-(5-fluoro-3-pyridinyl)-3-methyl-4-quinolinyl)amino)-5-(4-morpholinyl)phenyl)acetamide as a yellow amorphous solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.63 (1H, s), 8.65-8.79 (3H, m), 8.18 (1H, m), 8.02 (1H, m), 7.73 (1H, m), 7.50 (1H, m), 6.70 (1H, s), 6.55 (1H, s), 6.23 (1H, s), 3.66-3.78 (4H, m), 2.94-3.06 (4H, m), 2.14 (3H, s), 1.96 (3H, s). Mass Spectrum (ESI) m/e=490.1 (M+1).

Workup

  1. customPrepared
  2. customPurification by column chromatography (silica; 0-4% methanol in DCM)

Sources & evidence

ORD record
ord-116aaff273144f81a59aab129ca54494
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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