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

HRID 1431780Notes

Reaction equation

HRID 1431780 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:47])=[CH:43][C:44]=2[F:46])[N:39]=[C:38]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][N:49]=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:44]1[CH:43]=[C:42]([F:47])[CH:41]=[C:40]2[C:45]=1[C:36]([NH:55][C:56]1[CH:57]=[C:58]([NH:68][C:69](=[O:71])[CH3:70])[CH:59]=[C:60]([N:62]3[CH2:67][CH2:66][O:65][CH2:64][CH2:63]3)[CH:61]=1)=[C:37]([CH3:54])[C:38]([C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][N:49]=1)=[N:39]2

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596310254-Chloro-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolineHCID 67507700N-(3-amino-5-morpholinophenyl)acetamide

Product 1

HCID 59631318N-(3-((5,7-difluoro-3-methyl-2-(2-pyridinyl)-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 (1.5 mg, 6.88 μmol), XPhos (9.9 mg, 0.021 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinoline (0.040 g, 0.138 mmol), N-(3-amino-5-morpholinophenyl)acetamide (0.034 g, 0.144 mmol), potassium carbonate (0.048 g, 0.344 mmol), and tert-butanol at 110° C. for 2 h. Purification by reverse-phase HPLC (0-70% acetonitrile in water) afforded N-(3-((5,7-difluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)amino)-5-(4-morpholinyl)phenyl)acetamide as a yellow amorphous solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.69 (1H, dq, J=4.8, 1.0 Hz), 7.80-7.95 (3H, m), 7.59 (1H, ddt, J=9.6, 2.2, 1.0, 1.0 Hz), 7.37-7.44 (1H, m), 7.12-7.22 (2H, m), 7.01 (1H, ddd, J=13.8, 8.5, 2.5 Hz), 6.31-6.36 (1H, m), 6.23 (1H, t, J=2.2 Hz), 3.81-3.87 (4H, m), 3.15-3.22 (4H, m), 2.12 (3H, s), 2.10 (3H, s). Mass Spectrum (ESI) m/e=490.0 (M+1).

Workup

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

Sources & evidence

ORD record
ord-03ee0fb81754413c9a4cfa8ea6ad6d43
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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