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

HRID 1257144Notes

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][NH:25][CH3:26]>C1COCC1>[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]([N:25]([CH3:26])[CH3:24])[CH:12]=3)[CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of Example A3 (0.25 g, 0.710 mmol) in THF (6 mL) was treated with dimethylamine (2M in THF, 2.84 mL, 5.68 mmol) and heated at 80° C. overnight. Additional dimethylamine (2M in THF, 5.68 mL, 11.36 mmol) was added over 3 days and the reaction mixture was heated at 80° C. The mixture was partitioned between DCM and satd. NaHCO3 and extracted with DCM (3×). The combined organic extracts were dried (MgSO4) and evaporated. The crude product was purified by silica gel chromatography (EtOAc/Hex) to give 3-(5-amino-2-chloro-4-fluorophenyl)-7-(dimethylamino)-1-ethyl-1,6-naphthyridin-2(1H)-one (0.21 g, 82% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.45 (s, 1H), 7.69 (s, 1H), 7.18 (d, 1H), 6.73 (d, 1H), 6.29 (s, 1H), 5.31 (br s, 2H), 4.21 (q, 2H), 3.14 (s, 6H), 1.18 (t, 3H); MS (ESI) m/z: 361.1 [M+H]+.

Workup

temperaturethe reaction mixture was heated at 80° C
customThe mixture was partitioned between DCM and satd
extractionNaHCO3 and extracted with DCM (3×)
dry with materialThe combined organic extracts were dried (MgSO4)
customevaporated
customThe crude product was purified by silica gel chromatography (EtOAc/Hex)

Sources & evidence

ORD record: ord-5e183b0f19024c538d52a4fb06d21ed5
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08461179B1

Reaction notes

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