Dimethylformamide → 3-(5-amino-2-chloro-4-fluorophenyl)-7-(2-(dimethylamino)ethylamino)-1-ethyl-1,6-naphthyridin-2(1H)-one

HRID 1257142Notes

Reaction equation

[NH2:1][C:2]1[C:3]([F:23])=[CH:4][C:5]([Cl:22])=[C:6]([C:8]2[C:9](=[O:21])[N:10]([CH2:19][CH3:20])[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13](Cl)[CH:12]=3)[CH:7]=1.[CH3:24][N:25]([CH3:29])[CH:26](N)[CH3:27].C[N:31](C=O)C>O>[NH2:1][C:2]1[C:3]([F:23])=[CH:4][C:5]([Cl:22])=[C:6]([C:8]2[C:9](=[O:21])[N:10]([CH2:19][CH3:20])[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13]([NH:31][CH2:27][CH2:26][N:25]([CH3:29])[CH3:24])[CH:12]=3)[CH:7]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of Example A3 (1.00 g, 2.84 mmol) in DMF (10 mL) was added N,N-dimethylethanediamine (0.250 g, 2.84 mmol) and the resulting reaction mixture was heated at 100° C. for 36 h. The reaction mixture was diluted with water and extracted with EtOAc (3×). The combined organic layers were washed with brine, dried (MgSO4), and the solvent evaporated. The residue was crystallized from IPA to provide 3-(5-amino-2-chloro-4-fluorophenyl)-7-(2-(dimethylamino)ethylamino)-1-ethyl-1,6-naphthyridin-2(1H)-one (0.98 g, 85% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 8.36 (s, 1H), 7.64 (s, 1H), 7.17 (d, J=11 Hz, 1H), 6.84 (m, 1H), 6.72 (d, J=9 Hz, 1H), 6.37 (s, 1H), 5.30 (s, 2H), 4.08 (m, 2H), 3.40 (m, 2H), 2.41 (t, J=6 Hz, 2H), 2.20 (s, 6H), 1.18 (t, J=6 Hz, 3H); MS (ESI) m/z: 404.2 [M+H]+.

Workup

customthe resulting reaction mixture
extractionextracted with EtOAc (3×)
washThe combined organic layers were washed with brine
dry with materialdried (MgSO4)
customthe solvent evaporated
customThe residue was crystallized from IPA

Sources & evidence

ORD record: ord-edebec202822451f90cfb0559e17b8da
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08461179B1

Reaction notes

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