Potassium Iodide → HCID 58280079, compound

HRID 2189117Notes

Reaction equation

HRID 2189117 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:17]3[C:16]([NH:18][CH:19]4[CH2:24][CH2:23][CH2:22][NH:21][CH2:20]4)=[N:15][CH:14]=[N:13][C:12]=3[O:11][C:10]=2[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:5][CH:4]=1.CCN(C(C)C)C(C)C.[I-].[K+].[CH3:42][O:43][C:44](=[O:49])[CH2:45][CH2:46][CH2:47]Br>C1COCC1.O>[CH3:42][O:43][C:44](=[O:49])[CH2:45][CH2:46][CH2:47][N:21]1[CH2:22][CH2:23][CH2:24][CH:19]([NH:18][C:16]2[C:17]3[C:9]([C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=4)=[C:10]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[O:11][C:12]=3[N:13]=[CH:14][N:15]=2)[CH2:20]1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 81531DiisopropylethylamineHCID 107604Methyl 4-bromobutyrateHCID 58280153HCID 58280153, compound

Product 1

HCID 58280079HCID 58280079, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Heat a mixture of 100 mg (0.25 mmol) of (+/−)-5-(4-methoxyphenyl)-6-phenyl-N-piperidin-3-yl-furo[2,3-d]pyrimidin-4-amine (Example 39A), 65 μl (0.375 mmol) of DIEA, 4.1 mg (0.025 mmol) of potassium iodide and 45 mg (0.25 mmol) of 4-bromobutyric acid methyl ester in 2 ml of THF under reflux for 1 h. After cooling, add the reaction mixture to water and extract three times with ethyl acetate. Wash the combined organic phases twice with buffer solution (pH 7) and saturated sodium chloride solution, dry over magnesium sulphate and concentrate under reduced pressure. Purify the crude product by preparative RP-HPLC (eluent: acetonitrile/water gradient), followed by chromatography on silica gel (eluent: dichloromethane→dichloromethane/methanol 50:1). After stirring the resulting product with methanol, the precipitate is filtered off with suction, washed with a little methanol and dried under high vacuum. 58 mg (46.4% of theory) of the target product are isolated.

Workup

  1. temperatureHeat
  2. temperatureunder reflux for 1 h
  3. temperatureAfter cooling
  4. extractionextract three times with ethyl acetate
  5. washWash the combined organic phases twice with buffer solution (pH 7) and saturated sodium chloride solution
  6. dry with materialdry over magnesium sulphate
  7. concentrationconcentrate under reduced pressure
  8. customPurify the crude product by preparative RP-HPLC (eluent: acetonitrile/water gradient)
  9. filtrationthe precipitate is filtered off with suction
  10. washwashed with a little methanol
  11. customdried under high vacuum
  12. custom58 mg (46.4% of theory) of the target product are isolated

Sources & evidence

ORD record
ord-ff34b8ca2854497abb39f05142866901
Source dataset
uspto-grants-2012_12
Patent number
US08324222B2

Reaction notes

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