Hydrochloric Acid → 1-[2-(Dimethylamino)-2-oxoethyl]-7-[(4-fluorophenyl)methyl]-4-hydroxy-N-[2-(methyloxy)ethyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide

HRID 2364197Notes

Reaction equation

[CH3:1][N:2]([CH3:31])[C:3](=[O:30])[CH2:4][N:5]1[C:14]2[C:9](=[N:10][CH:11]=[C:12]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[CH:13]=2)[C:8]([OH:23])=[C:7]([C:24](OCC)=[O:25])[C:6]1=[O:29].[CH3:32][O:33][CH2:34][CH2:35][NH2:36].Cl>CN1C(=O)CCC1.O>[CH3:31][N:2]([CH3:1])[C:3](=[O:30])[CH2:4][N:5]1[C:14]2[C:9](=[N:10][CH:11]=[C:12]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[CH:13]=2)[C:8]([OH:23])=[C:7]([C:24]([NH:36][CH2:35][CH2:34][O:33][CH3:32])=[O:25])[C:6]1=[O:29]

Participants

Conditions

Temperature: 105 °C

Procedure

A mixture of ethyl 1-[2-(dimethylamino)-2-oxoethyl]-7-[(4-fluorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate(49.2 g, 115 mmol) and 2-methoxyethylamine (14.8 mL, 172 mmol) in NMP (400 mL) was heated at 95-115° C. for 1-2 h. The mixture was cooled to rt, diluted with water (600 mL) and acidified with 1N HCl (72 mL). The precipitate was collected by filtration, washed with water and dried overnight in a vacuum oven to afford the product as a white solid: 1H NMR (d6-DMSO) δ 10.23 (1H, br t, J=5 Hz), 8.51 (1H, s), 7.75 (1H, s), 7.32 (2H, dd, J=9, 6 Hz), 7.12 (2H, t, J=9 Hz), 5.12 (2H, s), 4.11 (2H, s), 3.54-3.44 (4H, m), 3.27 (3H, s), 3.12 (3H, s), 2.82 (3H, s); HRMS calcd for C23H25FN4O5+H+: 457.1887.Found: 457.1884.

Workup

temperatureThe mixture was cooled to rt
filtrationThe precipitate was collected by filtration
washwashed with water
customdried overnight in a vacuum oven

Sources & evidence

ORD record: ord-a37c1b8af56143eb8a6bd51b47630512
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08691991B2

Reaction notes

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