Potassium Carbonate → N-(3-((2-(3,5-difluorophenyl)-3-methyl-1,8-naphthyridin-4-yl)amino)-5-(4-morpholinyl)phenyl)acetamide

HRID 1431788Notes

Reaction equation

HRID 1431788 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([NH:14][C:15](=[O:17])[CH3:16])[CH:5]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH:7]=1.Cl[C:19]1[C:28]2[C:23](=[N:24][CH:25]=[CH:26][CH:27]=2)[N:22]=[C:21]([C:29]2[CH:34]=[C:33]([F:35])[CH:32]=[C:31]([F:36])[CH:30]=2)[C:20]=1[CH3:37].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(O)(C)(C)C>[F:36][C:31]1[CH:30]=[C:29]([C:21]2[C:20]([CH3:37])=[C:19]([NH:1][C:2]3[CH:3]=[C:4]([NH:14][C:15](=[O:17])[CH3:16])[CH:5]=[C:6]([N:8]4[CH2:13][CH2:12][O:11][CH2:10][CH2:9]4)[CH:7]=3)[C:28]3[C:23](=[N:24][CH:25]=[CH:26][CH:27]=3)[N:22]=2)[CH:34]=[C:33]([F:35])[CH:32]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596315174-Chloro-2-(3,5-difluorophenyl)-3-methyl-1,8-naphthyridineHCID 67507700N-(3-amino-5-morpholinophenyl)acetamide

Product 1

HCID 59631457N-(3-((2-(3,5-difluorophenyl)-3-methyl-1,8-naphthyridin-4-yl)amino)-5-(4-morpholinyl)phenyl)acetamide

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6386tert-ButanolSolvent

Procedure

Prepared according to Procedure X by stirring N-(3-amino-5-morpholinophenyl)-acetamide (48.6 mg, 0.206 mmol), 4-chloro-2-(3,5-difluorophenyl)-3-methyl-1,8-naphthyridine (50 mg, 0.172 mmol), palladium (II) acetate (3.9 mg, 0.017 mmol), XPhos (16.4 mg, 0.034 mmol), potassium carbonate (60 mg, 0.43 mmol), and 1 mL tert-butanol at 85° C. for 24 h. Purification by reverse-phase HPLC afforded N-(3-((2-(3,5-difluorophenyl)-3-methyl-1,8-naphthyridin-4-yl)amino)-5-(4-morpholinyl)phenyl)acetamide. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.84 (1H, dd, J=4.1, 2.0 Hz), 8.21-8.28 (2H, m), 7.23-7.27 (1H, m), 7.10-7.14 (1H, m), 7.04-7.10 (2H, m), 6.85-6.91 (1H, m), 6.45-6.50 (1H, m), 6.14-6.21 (2H, m), 3.77-3.86 (4H, m), 3.09-3.15 (4H, m), 2.33 (3H, s), 1.99 (3H, s). Mass Spectrum (ESI) m/e=490.0 (M+1).

Workup

  1. customPrepared
  2. customPurification by reverse-phase HPLC

Sources & evidence

ORD record
ord-f3ffe47f76d345b1bc8d6cd199a6a565
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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