Sodium t-butoxide → 3-methyl-N-(5-(4-morpholinyl)-3-pyridinyl)-2-(2-pyridinyl)-1,8-naphthyridin-4-amine

HRID 1431708Notes

Reaction equation

HRID 1431708 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]=[CH:16][CH:15]=[CH:14][N:13]=2)[C:3]=1[CH3:18].[O:19]1[CH2:24][CH2:23][N:22]([C:25]2[CH:26]=[C:27]([NH2:31])[CH:28]=[N:29][CH:30]=2)[CH2:21][CH2:20]1.CC(C)([O-])C.[Na+]>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+].C1(C)C=CC=CC=1>[CH3:18][C:3]1[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)=[N:5][C:6]2[C:11]([C:2]=1[NH:31][C:27]1[CH:28]=[N:29][CH:30]=[C:25]([N:22]3[CH2:23][CH2:24][O:19][CH2:20][CH2:21]3)[CH:26]=1)=[CH:10][CH:9]=[CH:8][N:7]=2

Participants

6

Reactant 3

HCID 23676156Sodium t-butoxideHCID 583477375-Morpholinopyridin-3-amineHCID 596310684-Chloro-3-methyl-2-(pyridin-2-yl)-1,8-naphthyridine

Product 1

HCID 596313703-methyl-N-(5-(4-morpholinyl)-3-pyridinyl)-2-(2-pyridinyl)-1,8-naphthyridin-4-amine

Reagents, catalysts & solvents 2

HCID 54751079XPhos PalladacycleCatalystHCID 1140TolueneSolvent

Procedure

To a stirred solution of 4-chloro-3-methyl-2-(pyridin-2-yl)-1,8-naphthyridine (70 mg, 0.27 mmol), 5-morpholinopyridin-3-amine (49 mg, 0.27 mmol) and XPhos precatalyst (20 mg, 0.027 mmol) in toluene (4 mL) was added sodium tert-butoxide (52 mg, 0.55 mmol) and the reaction was heated at reflux for 2 h. After this time the reaction was allowed to cool to rt and partitioned between EtOAc (60 mL) and water (20 mL). The separated organic layer was dried over MgSO4, filtered and evaporated in vacuo. Purification by reverse phase HPLC gave 3-methyl-N-(5-(4-morpholinyl)-3-pyridinyl)-2-(2-pyridinyl)-1,8-naphthyridin-4-amine. H NMR (400 MHz, CDCl3) δ ppm 9.03 (1H, dd, J=4.1, 2.0 Hz), 8.69 (1H, ddd, J=4.8, 1.7, 1.1 Hz), 8.20 (1H, dd, J=8.3, 1.9 Hz), 8.08 (1H, dt, J=7.9, 1.1 Hz), 7.84-7.93 (2H, m), 7.78 (1H, d, J=2.3 Hz), 7.31-7.42 (2H, m), 6.51-6.61 (1H, m), 6.37 (1H, t, J=2.4 Hz), 3.74-3.87 (4H, m), 3.00-3.10 (4H, m), 2.47 (3H, s). Mass Spectrum (ESI) m/e=399.2 (M+1).

Workup

  1. temperaturethe reaction was heated
  2. temperatureat reflux for 2 h
  3. custompartitioned between EtOAc (60 mL) and water (20 mL)
  4. dry with materialThe separated organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customPurification by reverse phase HPLC

Sources & evidence

ORD record
ord-fa23f99980484dccaf1371d1ab3ad735
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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