Sodium Hydroxide → 6-chloro-2-(2-chlorophenyl)-1,7-naphthyridin-4(1H)-one

HRID 468845Notes

Reaction equation

C(OC([NH:8][C:9]1[C:14]([C:15](O)=[O:16])=[CH:13][C:12]([Cl:18])=[N:11][CH:10]=1)=O)(C)(C)C.[Cl:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[C:26](=O)[CH3:27].[OH-].[Na+]>O>[Cl:18][C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][N:11]=1)[NH:8][C:26]([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[Cl:19])=[CH:27][C:15]2=[O:16]

Participants

Conditions

Temperature: 150 °C

Procedure

5-(tert-Butoxycarbonylamino)-2-chloroisonicotinic acid (502 mg, 1.84 mmol) was suspended in polyphosphoric acid (9.5 g, 102 mmol) at ambient temperature and stirred for 10 mins causing a bright yellow coloration and visible evolution of gas. 2′-Chloroacetophenone (570 mg, 3.69 mmol) was added and the mixture heated to 150° C. for 2.5 h. The mixture was diluted with cold water (50 mL), and then cooled in ice and treated with solid sodium hydroxide (6.0 g, 150 mmol) to pH ˜7. The mixture was filtered and the recovered oily solids washed with water, dissolved in methanol and reconcentrated in vacuo. The residue was purified by flash chromatography (silica, ISCO, 0.5-20% methanol in DCM) to afford the title compound as a cream solid (29.2 mg, 5.5%). 1H NMR (400 MHz, MeOD) δ 8.87 (s, 1H), 8.12 (s, 1H), 7.64-7.58 (m, 2H), 7.58-7.46 (m, 2H), 6.47 (s, 1H); NH absent. LCMS: M+H+=291 & 293.

Workup

temperaturecooled in ice
filtrationThe mixture was filtered
washthe recovered oily solids washed with water
dissolutiondissolved in methanol
customThe residue was purified by flash chromatography (silica, ISCO, 0.5-20% methanol in DCM)

Sources & evidence

ORD record: ord-b423f559a19f440a9c7c12cf91b2ac8d
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08623889B2

Reaction notes

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