Potassium Iodide → HCID 86723820, compound

HRID 577591Notes

Reaction equation

HRID 577591 reaction equation
[Cl:1][C:2]1[C:3]([O:12][CH:13]([CH3:15])[CH3:14])=[CH:4][CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[NH:8][CH2:7]2.C([O:23][C:24]1[C:29]([CH2:30]Cl)=[C:28]([CH3:32])[CH:27]=[C:26]([CH3:33])[N:25]=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[K+]>CN(C=O)C>[Cl:1][C:2]1[C:3]([O:12][CH:13]([CH3:15])[CH3:14])=[CH:4][CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH2:30][C:29]1[C:24](=[O:23])[NH:25][C:26]([CH3:33])=[CH:27][C:28]=1[CH3:32])[CH2:7]2

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 612578682-(Benzyloxy)-3-(chloromethyl)-4,6-dimethylpyridineHCID 86723819HCID 86723819, compound

Product 1

HCID 86723820HCID 86723820, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 7-chloro-6-isopropoxy-2,3-dihydro-isoindol-1-one (133a, 120 mg, 0.532 mmol), 2-benzyloxy-3-chloromethyl-4,6-dimethyl-pyridine (Cpd Z, 139 mg, 0.532 mmol), cesium carbonate (260 mg, 0.798 mmol), and potassium iodide (132 mg, 0.798 mmol) in DMF (6 mL) was stirred at 100° C. overnight. The solution was cooled to room temperature and the reaction mixture partitioned between ethyl acetate (50 mL) and water (50 mL). The organic phase was separated, washed with water (50 mL) and brine (50 mL), dried over sodium sulfate and concentrated under vacuum. The residue was purified by column chromatography (silica gel, heptanes/EtOAc) and the residue concentrated under vacuum. The residue was treated with TFA at room temperature overnight. Excess TFA was removed under vacuum and the resulting residue was partitioned between ethyl acetate (50 mL) and sodium bicarbonate (50 mL). The organic phase was separated, washed with brine (50 mL), dried over sodium sulfate, and concentrated under vacuum. The residue was purified by column chromatography (silica gel, MeOH/EtOAc, 1/10) to give the title compound (Example 133, 20 mg, 12% yield over two steps) as a solid. 1H NMR (400 MHz, chloroform-d) δ 12.09 (br. s., 1H), 7.08-7.13 (m, 1H), 7.02-7.07 (m, 1H), 5.94 (s, 1H), 4.66 (s, 2H), 4.44-4.55 (m, 1H), 4.31 (s, 2H), 2.37 (s, 3H), 2.24 (s, 3H), 1.36 (d, J=6.06 Hz, 6H): MS 361 [M+H].

Workup

  1. temperatureThe solution was cooled to room temperature
  2. customthe reaction mixture partitioned between ethyl acetate (50 mL) and water (50 mL)
  3. customThe organic phase was separated
  4. washwashed with water (50 mL) and brine (50 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by column chromatography (silica gel, heptanes/EtOAc)
  8. concentrationthe residue concentrated under vacuum
  9. additionThe residue was treated with TFA at room temperature overnight
  10. customExcess TFA was removed under vacuum
  11. customthe resulting residue was partitioned between ethyl acetate (50 mL) and sodium bicarbonate (50 mL)
  12. customThe organic phase was separated
  13. washwashed with brine (50 mL)
  14. dry with materialdried over sodium sulfate
  15. concentrationconcentrated under vacuum
  16. customThe residue was purified by column chromatography (silica gel, MeOH/EtOAc, 1/10)

Sources & evidence

ORD record
ord-1e0e38ce1732403aa611d9665aa86b92
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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