(1,1'-Biphenyl)-2-ol → 2-[1,2,4]Triazolo[1,5-a]pyridin-6-yl-malonic acid diethyl ester

HRID 1921610Notes

Reaction equation

[C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].I[C:13]1[CH:14]=[CH:15][C:16]2[N:17]([N:19]=[CH:20][N:21]=2)[CH:18]=1.C1(C2C=CC=CC=2)C(O)=CC=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1COCC1.[Cu](I)I>[CH2:10]([O:9][C:1](=[O:8])[CH:2]([C:13]1[CH:14]=[CH:15][C:16]2[N:17]([N:19]=[CH:20][N:21]=2)[CH:18]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4])[CH3:11]

Participants

Conditions

Temperature: 70 °C

Procedure

Diethyl malonate (400 μL) was added to a mixture of 6-iodo-[1,2,4]triazolo[1,5-a]pyridine (245 mg, 1 mmol), copper iodide (19 mg, 0.1 mmol), biphenyl-2-ol (34 mg, 0.2 mmol), and Cs2CO3 in THF (5 mL). The heterogeneous solution was stirred for 16 h at 70° C. After cooling, the mixture was partitioned between chloroform (40 mL) and aq NH4Cl (20 mL). The organic layer was washed with NH4Cl (3×15 mL), NaHCO3 (20 mL), and brine (20 mL) then was dried over Na2SO4. Concentration of the solution followed by SiO2 flash chromatography purification yielded the product (170 mg, 61%) as a colorless glass. 1H-NMR (CDCl3): δ 8.77 (1H, m), 8.37 (1H, s), 7.78 (1H, dd, J=0.9, 9.1 Hz), 7.69 (1H, dd, J=1.8, 9.3 Hz), 4.76 (1H, s), 4.27 (4H, m), 1.30 (6H, t, J=7.3 Hz). ESI-MS (m/z): Calcd. for C13H15N3O4: 277.1; found: 278.2 (M+H).

Workup

temperatureAfter cooling
customthe mixture was partitioned between chloroform (40 mL) and aq NH4Cl (20 mL)
washThe organic layer was washed with NH4Cl (3×15 mL), NaHCO3 (20 mL), and brine (20 mL)
dry with materialthen was dried over Na2SO4
customConcentration of the solution followed by SiO2 flash chromatography purification

Sources & evidence

ORD record: ord-72a0eabf935f4a9ca7a11026fb7ecd1d
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08173654B2

Reaction notes

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