Cesium carbonate → 5-Fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one

HRID 1617268Notes

Reaction equation

[F:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([CH2:13][C:14]3[N:18]([CH3:19])[N:17]=[CH:16][N:15]=3)=[N:7][NH:8][C:9]2=[O:12])=[C:4](/[N:20]=[CH:21]/[C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1COCC1.O>[F:1][C:2]1[CH:3]=[C:4]2[NH:20][CH:21]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[CH:13]([C:14]3[N:18]([CH3:19])[N:17]=[CH:16][N:15]=3)[C:6]3=[N:7][NH:8][C:9](=[O:12])[C:10]([CH:11]=1)=[C:5]23

Participants

Conditions

Temperature: 55 °C

Procedure

To a suspension of (E)-7-fluoro-5-(4-fluorobenzylideneamino)-4-((1-methyl-1H-1,2,4-triazol-5-yl)methyl)phthalazin-1(2H)-one (8) (2.0 g, 5.3 mmol) in THF (80 mL) was added cesium carbonate (3.4 g, 10.6 mmol). The reaction mixture was stirred at 55° C. for 4 hours and cooled down to room temperature. The mixture was diluted with water (50 ml) and extracted with ethyl acetate (50 mL×3). The combined organic layers were dried over anhydrous Na2SO4 and evaporated to dryness to afford the title compound as a white solid (1.6 g, yield 80%). LC-MS (ESI) m/z: 381 (M+1)+. 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 3.66 (s, 3H), 4.97-5.04 (m, 2H), 6.91-6.94 (dd, J1=2.4, J2=11.2 Hz, 1H), 7.06-7.09 (dd, J1=2.4, J2=8.8 Hz, 1H), 7.14-7.18 (m, 3H), 7.47-7.51 (m, 2H), 7.72 (s, 1H), 7.80 (s, 1H), 12.35 (s, 1H).

Workup

temperaturecooled down to room temperature
extractionextracted with ethyl acetate (50 mL×3)
dry with materialThe combined organic layers were dried over anhydrous Na2SO4
customevaporated to dryness

Sources & evidence

ORD record: ord-b65fa57c242a4f639609de3ac95fcc49
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08765945B2

Reaction notes

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