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

HRID 1431707Notes

Reaction equation

HRID 1431707 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:31]=[CH:30][C:29]([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)=[CH:28][C:26]=2[NH2:27])[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>[N:22]1([C:25]2[CH:31]=[CH:30][C:29]([N:32]3[CH2:33][CH2:34][O:35][CH2:36][CH2:37]3)=[CH:28][C:26]=2[NH:27][C:2]2[C:11]3[C:6](=[N:7][CH:8]=[CH:9][CH:10]=3)[N:5]=[C:4]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)[C:3]=2[CH3:18])[CH2:23][CH2:24][O:19][CH2:20][CH2:21]1

Participants

6

Reactant 3

HCID 23676156Sodium t-butoxideHCID 288098152,5-DimorpholinobenzenamineHCID 596310684-Chloro-3-methyl-2-(pyridin-2-yl)-1,8-naphthyridine

Product 1

HCID 59631158N-(2,5-di-4-morpholinylphenyl)-3-methyl-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 (48.6 mg, 0.19 mmol), 2,5-dimorpholinoaniline (50 mg, 0.19 mmol) and XPhos precatalyst (14 mg, 0.019 mmol) in toluene (4 mL) was added sodium tert-butoxide (36 mg, 0.38 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 N-(2,5-di-4-morpholinylphenyl)-3-methyl-2-(2-pyridinyl)-1,8-naphthyridin-4-amine. H NMR (500 MHz, CDCl3) δ ppm 9.08 (1H, dd, J=3.9, 1.7 Hz), 8.71 (1H, br. s.), 8.26 (1H, dd, J=8.3, 1.7 Hz), 8.16 (1H, d, J=7.8 Hz), 7.88-7.96 (1H, m), 7.39 (2H, dd, J=8.3, 4.2 Hz), 7.11 (1H, d, J=8.8 Hz), 6.45 (1H, dd, J=8.7, 2.6 Hz), 5.99 (1H, d, J=2.7 Hz), 3.90 (4H, t, J=4.4 Hz), 3.66-3.77 (4H, m), 3.05 (4H, br. s.), 2.82-2.93 (4H, m), 2.51 (3H, s). Mass Spectrum (ESI) m/e=483.2 (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-0b45eb71562e4d5a8419dfdaa183faa1
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

Loading…