Potassium Carbonate → N-(3-((2-(4,4-dimethyl-2-oxo-1-pyrrolidinyl)-7-fluoro-3-methyl-4-quinolinyl)amino)-5-(4-morpholinyl)phenyl)acetamide

HRID 1431779Notes

Reaction equation

HRID 1431779 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]([N:47]2[CH2:51][C:50]([CH3:53])([CH3:52])[CH2:49][C:48]2=[O:54])[C:37]=1[CH3:55].[NH2:56][C:57]1[CH:58]=[C:59]([NH:69][C:70](=[O:72])[CH3:71])[CH:60]=[C:61]([N:63]2[CH2:68][CH2:67][O:66][CH2:65][CH2:64]2)[CH:62]=1.C(=O)([O-])[O-].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(O)(C)(C)C>[CH3:52][C:50]1([CH3:53])[CH2:51][N:47]([C:38]2[C:37]([CH3:55])=[C:36]([NH:56][C:57]3[CH:58]=[C:59]([NH:69][C:70](=[O:72])[CH3:71])[CH:60]=[C:61]([N:63]4[CH2:68][CH2:67][O:66][CH2:65][CH2:64]4)[CH:62]=3)[C:45]3[C:40](=[CH:41][C:42]([F:46])=[CH:43][CH:44]=3)[N:39]=2)[C:48](=[O:54])[CH2:49]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596313401-(4-Chloro-7-fluoro-3-methylquinolin-2-yl)-4,4-dimethylpyrrolidin-2-oneHCID 67507700N-(3-amino-5-morpholinophenyl)acetamide

Product 1

HCID 59631193N-(3-((2-(4,4-dimethyl-2-oxo-1-pyrrolidinyl)-7-fluoro-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 (0.4 mg, 1.743 μmol), XPhos (2.5 mg, 5.23 μmol), 1-(4-chloro-7-fluoro-3-methylquinolin-2-yl)-4,4-dimethylpyrrolidin-2-one (0.018 g, 0.058 mmol), N-(3-amino-5-morpholinophenyl)acetamide (0.0164 g, 0.070 mmol), potassium carbonate (0.020 g, 0.145 mmol), and tert-butanol (0.5 mL) at 110° C. for 30 minutes. Purification by reverse-phase HPLC (0-70% acetonitrile in water) afforded N-(3-((2-(4,4-dimethyl-2-oxo-1-pyrrolidinyl)-7-fluoro-3-methyl-4-quinolinyl)amino)-5-(4-morpholinyl)phenyl)acetamide as a yellow amorphous solid. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.79 (1H, br. s.), 7.55 (2H, d, J=9.0 Hz), 7.13 (1H, t). 6.88 (1H, br. s.), 6.39 (1H, br. s.), 6.34 (1H, br. s.), 6.06 (1H, br. s.), 3.88 (2H, br. s.), 3.70-3.81 (4H, m), 2.98-3.15 (4H, m), 2.46 (2H, s), 2.13 (3H, br. s.), 2.09 (3H, s), 1.33 (6H, s). Mass Spectrum (ESI) m/e=506.2 (M+1).

Workup

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

Sources & evidence

ORD record
ord-f61e7d99cb754163aaa2935e232d8109
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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