Dimethyl Sulfoxide → 4-(6-tert-Butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-chloro-pyridine-3-carbaldehyde

HRID 337319Notes

Reaction equation

HRID 337319 reaction equation
[Cl:1][C:2]1[N:9]=[CH:8][CH:7]=[C:6](I)[C:3]=1[CH:4]=[O:5].[C:11]([C:15]1[CH:16]=[C:17]2[C:22](=[C:23]([F:25])[CH:24]=1)[C:21](=[O:26])[NH:20][N:19]=[CH:18]2)([CH3:14])([CH3:13])[CH3:12].C(=O)([O-])[O-].[K+].[K+].CS(C)=O>O.[Cu]I>[C:11]([C:15]1[CH:16]=[C:17]2[C:22](=[C:23]([F:25])[CH:24]=1)[C:21](=[O:26])[N:20]([C:6]1[CH:7]=[CH:8][N:9]=[C:2]([Cl:1])[C:3]=1[CH:4]=[O:5])[N:19]=[CH:18]2)([CH3:14])([CH3:12])[CH3:13]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 11430Potassium CarbonateHCID 100386372-Chloro-4-iodopyridine-3-carbaldehydeHCID 594737656-(tert-Butyl)-8-fluorophthalazin-1(2H)-one

Product 1

HCID 866769374-(6-tert-Butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-chloro-pyridine-3-carbaldehydeYield 52%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

In a 50 mL round-bottomed flask, 2-chloro-4-iodonicotinaldehyde (389 mg, 1.45 mmol, Eq: 1.6), 6-tert-butyl-8-fluorophthalazin-1(2H)-one (200 mg, 908 μmol, Eq: 1.00) and potassium carbonate (251 mg, 1.82 mmol, Eq: 2) were combined with DMSO (8 ml) to give a yellow solution. The solution was degassed for 5 min with argon. Copper(I) iodide (173 mg, 908 μmol, Eq: 1.00) was added. The reaction mixture was heated to 110° C. and stirred for 2 h and the reaction was allowed to cool to room temperature. The reaction was diluted with 1:1 H2O/sat. NH4Cl (80 mL) and the resulting solid collected by filtration. The solid was washed several times with 1:1 H2O/sat. NH4Cl, then water (2×) and then EtOAc:hexanes (3:1, 2×). A lot of color in the organic phase. A brown solid remained. Solid was washed with EtOAc and then CH2Cl2 several times. The combined organic extracts were washed with water, dried over MgSO4 and concentrated in vacuo. The resulting residue was purified by flash chromatography (silica gel, 40 g, 5% to 30% EtOAc in hexanes) to afford the desired product (170 mg) as a white solid. (M+H)+=360 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.42 (s, 9 H) 7.40-7.65 (m, 3 H) 8.24 (d, J=2.64 Hz, 1 H) 8.66 (d, J=5.29 Hz, 1 H) 10.32 (s, 1 H).

Workup

  1. customto give a yellow solution
  2. customThe solution was degassed for 5 min with argon
  3. temperatureto cool to room temperature
  4. filtrationNH4Cl (80 mL) and the resulting solid collected by filtration
  5. washThe solid was washed several times with 1:1 H2O/
  6. washSolid was washed with EtOAc
  7. washThe combined organic extracts were washed with water
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo
  10. customThe resulting residue was purified by flash chromatography (silica gel, 40 g, 5% to 30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-30609744a1be4b47b7504818aba1046d
Source dataset
uspto-grants-2014_11
Patent number
US08889682B2

Reaction notes

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