Toluene → 2-(3,5-difluorophenyl)-N-(2,5-di-4-morpholinylphenyl)-3-methyl-1,8-naphthyridin-4-amine

HRID 1431451Notes

Reaction equation

HRID 1431451 reaction equation
Cl[C:2]1[C:11]2[C:6](=[N:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[C:14]([F:19])[CH:13]=2)[C:3]=1[CH3:20].C[C:22]1([CH3:37])[C:26]2=[N:27][CH:28]=[C:29]([N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)[CH:30]=[C:25]2[NH:24]C1.[CH3:38][C:39](C)([O-:41])C.[Na+].[C:44]1(C)C=CC=CC=1>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+]>[F:19][C:14]1[CH:13]=[C:12]([C:4]2[C:3]([CH3:20])=[C:2]([NH:24][C:25]3[CH:30]=[C:29]([N:31]4[CH2:32][CH2:33][O:34][CH2:35][CH2:36]4)[CH:37]=[CH:22][C:26]=3[N:27]3[CH2:28][CH2:44][O:41][CH2:39][CH2:38]3)[C:11]3[C:6](=[N:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)[CH:17]=[C:16]([F:18])[CH:15]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 23676156Sodium t-butoxideHCID 596315174-Chloro-2-(3,5-difluorophenyl)-3-methyl-1,8-naphthyridineHCID 672844994-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)-morpholine

Product 1

HCID 596314242-(3,5-difluorophenyl)-N-(2,5-di-4-morpholinylphenyl)-3-methyl-1,8-naphthyridin-4-amine

Reagents, catalysts & solvents 1

HCID 54751079XPhos PalladacycleCatalyst

Procedure

To a stirred solution of 4-chloro-2-(3,5-difluorophenyl)-3-methyl-1,8-naphthyridine (40 mg, 0.14 mmol), 4-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]-pyridin-6-yl)morpholine (32 mg, 0.14 mmol) and XPhos precatalyst (10 mg, 0.014 mmol) in toluene (4 mL) was added sodium tert-butoxide (26 mg, 0.27 mmol) and the reaction was heated at reflux for 2 h. Purification by reverse phase HPLC (10 to 60% acetonitrile in water) gave 2-(3,5-difluorophenyl)-N-(2,5-di-4-morpholinylphenyl)-3-methyl-1,8-naphthyridin-4-amine. H NMR (400 MHz, chloroform-d) δ ppm 9.10 (1H, dd, J=4.1, 2.0 Hz), 8.26 (1H, dd, J=8.4, 2.0 Hz), 7.40 (1H, dd, J=8.4, 4.1 Hz), 7.21-7.31 (2H, m), 7.13 (1H, d, J=8.6 Hz), 6.91-6.93 (1H, m), 6.48 (1H, dd, J=8.7, 2.6 Hz), 5.96 (1H, d, J=2.7 Hz), 3.91 (4H, t, J=4.6 Hz), 3.71-3.73 (4H, m), 3.05 (4H, br s), 2.87-2.90 (4H, m), 2.38 (3H, s). Mass Spectrum (ESI) m/e=518.2 (M+1).

Workup

  1. temperaturethe reaction was heated
  2. temperatureat reflux for 2 h
  3. customPurification by reverse phase HPLC (10 to 60% acetonitrile in water)

Sources & evidence

ORD record
ord-c98673f42dd04f15b0599918c5cba6a1
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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