Potassium Iodide → 2-[2-(4-fluoro-2,3-dihydroindol-1-yl)-2-oxoethyl]-6-chloro-3H-pyrimidin-4-one

HRID 2278540Notes

Reaction equation

HRID 2278540 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8]C)[N:5]=[C:4]([CH2:10][C:11]([N:13]2[C:21]3[C:16](=[C:17]([F:22])[CH:18]=[CH:19][CH:20]=3)[CH2:15][CH2:14]2)=[O:12])[N:3]=1.[I-].[K+].C(#N)C.C[Si](C)(C)Cl>CCOC(C)=O>[Cl:1][C:2]1[N:3]=[C:4]([CH2:10][C:11]([N:13]2[C:21]3[C:16](=[C:17]([F:22])[CH:18]=[CH:19][CH:20]=3)[CH2:15][CH2:14]2)=[O:12])[NH:5][C:6](=[O:8])[CH:7]=1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 6342AcetonitrileHCID 6397ChlorotrimethylsilaneHCID 866992651-(4-Fluoro-2,3-dihydroindol-1-yl)-2-(4-methoxy-6-chloropyrimidin-2-yl)ethanone

Product 1

HCID 1363786742-[2-(4-fluoro-2,3-dihydroindol-1-yl)-2-oxoethyl]-6-chloro-3H-pyrimidin-4-oneYield 59%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

2 g of 2-(4-chloro-6-methoxypyrimidin-2-yl)-1-(4-fluoro-2,3-dihydroindol-1-yl)ethanone (example 17b, step 1b), potassium iodide (3.1 g), 30 ml of acetonitrile and 2.03 g of trimethylchlorosilane are placed in a reactor suitable for microwave-heating. The reactor is closed and irradiated for 30 minutes at 100° C. and then left overnight at A.T. The reaction medium is diluted with EtOAc and then washed twice with water and then with brine. The organic phases are combined, dried over magnesium sulfate, filtered and evaporated. The product obtained is chromatographed on silica. Elution is then carried out with dichloromethane/methanol (from 100/0 to 95/5). The fractions containing the expected product are evaporated under reduced pressure. The compound obtained is triturated from methanol, filtered and dried. 2-(4-Chloro-6-oxopyrimidin-2-yl)-1-(4-fluoro-2,3-dihydroindol-1-yl) ethanone is isolated (1.13 g); yield=59% (LCMS ES+ retention time Tr (min)=1.04; [M+H]+: m/z 308).

Workup

  1. temperaturesuitable for microwave-heating
  2. customThe reactor is closed
  3. customirradiated for 30 minutes at 100° C.
  4. washwashed twice with water
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe product obtained
  9. customis chromatographed on silica
  10. washElution
  11. additionThe fractions containing the expected product
  12. customare evaporated under reduced pressure
  13. customThe compound obtained
  14. customis triturated from methanol
  15. filtrationfiltered
  16. customdried

Sources & evidence

ORD record
ord-180d77540ffa4ac6a5e6a73e1478be1d
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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