Acetophenone → 2-Phenyl-[1,6]naphthyridine-4-carboxylic acid

HRID 268593Notes

Reaction equation

C([O:3][C:4](=[O:20])[C:5]([C:7]1[CH:8]=[N:9][CH:10]=[CH:11][C:12]=1[NH:13]C(=O)C(C)(C)C)=O)C.[OH-].[K+].[C:23]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)(=O)[CH3:24]>C(O)C.[OH-].[Na+]>[C:26]1([C:23]2[CH:24]=[C:5]([C:4]([OH:20])=[O:3])[C:7]3[C:12](=[CH:11][CH:10]=[N:9][CH:8]=3)[N:13]=2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

Conditions

Temperature: 100 °C

Procedure

[4-(2,2-Dimethyl-propionylamino)-pyridin-3-yl]-oxo-acetic acid ethyl ester (532 mg, 1.91 mmol) was taken up in ethanol (1.9 mL) and 4N KOH (1.9 mL, 4 equiv) was added. The solution was refluxed for 2-3 h at 100° C., acetophenone (0.446 mL, 2.0 equiv) was added neat, and the reaction was allowed to reflux overnight. Upon cooling to room temperature, the solution was diluted with 1N NaOH and extracted twice with ether. The product was precipitated from the aqueous layer by the addition of glacial AcOH (5-10 mL). The solids were collected by vacuum filtration, rinsed with cold water, and dried under high vacuum (white solid, 371 mg, 78%). 1H NMR (400 MHz, DMSO-d6) δ 10.00 (s, 1 H), 8.80 (d, J=5.6 Hz, 1 H), 8.56 (s, 1 H), 8.35-8.31 (m, 2 H), 8.03 (d, J=6.0 Hz, 1 H), 7.61-7.58 (m, 3 H). MS (LR-APCI) calcd. for C15H11N2O2 (M+H) 251.1; found 251.5.

Workup

temperatureto reflux overnight
temperatureUpon cooling to room temperature
extractionextracted twice with ether
customThe product was precipitated from the aqueous layer by the addition of glacial AcOH (5-10 mL)
filtrationThe solids were collected by vacuum filtration
washrinsed with cold water
customdried under high vacuum (white solid, 371 mg, 78%)

Sources & evidence

ORD record: ord-5054df8c00204f88a0d86b3d4f805c73
Source dataset: uspto-grants-2008_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07446112B2

Reaction notes

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