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

HRID 1431777Notes

Reaction equation

HRID 1431777 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][CH2:50][CH2:49][C:48]2=[O:52])[C:37]=1[CH3:53].[NH2:54][C:55]1[CH:56]=[C:57]([NH:67][C:68](=[O:70])[CH3:69])[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:70])[CH3:69])[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]([N:47]3[CH2:51][CH2:50][CH2:49][C:48]3=[O:52])=[N:39]2)=[CH:44][CH:43]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596313861-(4-Chloro-7-fluoro-3-methylquinolin-2-yl)pyrrolidin-2-oneHCID 67507700N-(3-amino-5-morpholinophenyl)acetamide

Product 1

HCID 59631301N-(3-((7-fluoro-3-methyl-2-(2-oxo-1-pyrrolidinyl)-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 (0.3 mg, 1.417 μmol), XPhos (2.0 mg, 4.25 μmol), 1-(4-chloro-7-fluoro-3-methylquinolin-2-yl)pyrrolidin-2-one (0.020 g, 0.071 mmol), N-(3-amino-5-morpholinophenyl)-acetamide (0.020 g, 0.085 mmol), potassium carbonate (0.024 g, 0.177 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-((7-fluoro-3-methyl-2-(2-oxo-1-pyrrolidinyl)-4-quinolinyl)amino)-5-(4-morpholinyl)phenyl)acetamide as a yellow amorphous solid. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.80 (1H, dd, J=8.8, 7.3 Hz), 7.51-7.61 (1H, m), 7.45 (1H, br. s.), 7.08-7.19 (1H, m), 6.79-6.99 (1H, m), 6.37 (1H, br. s.), 6.25 (1H, br. s.), 6.05 (1H, br. s.), 4.13 (2H, d, J=7.1 Hz), 3.77 (4H, t, J=4.9 Hz), 3.08 (4H, t, J=4.9 Hz), 2.63 (2H, t, J=8.1 Hz), 2.23-2.36 (2H, m), 2.13 (3H, s), 2.06-2.10 (3H, m). Mass Spectrum (ESI) m/e=478.2 (M+1).

Workup

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

Sources & evidence

ORD record
ord-689704e014c449afbb036f5c7f032aa8
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

Loading…