Potassium Iodide → (+/-)-4-{3-[(5-Bromo-6-phenylfuro[2,3-d]pyrimidin-4-yl)oxy]piperidin-1-yl}butanoic acid methyl ester

HRID 2189056Notes

Reaction equation

HRID 2189056 reaction equation
[Br:1][C:2]1[C:10]2[C:9]([O:11][CH:12]3[CH2:17][CH2:16][CH2:15][NH:14][CH2:13]3)=[N:8][CH:7]=[N:6][C:5]=2[O:4][C:3]=1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[CH3:24][O:25][C:26](=[O:31])[CH2:27][CH2:28][CH2:29]Br.[I-].[K+].C(N(CC)C(C)C)(C)C>C1COCC1.ClCCl.O>[CH3:24][O:25][C:26](=[O:31])[CH2:27][CH2:28][CH2:29][N:14]1[CH2:15][CH2:16][CH2:17][CH:12]([O:11][C:9]2[C:10]3[C:2]([Br:1])=[C:3]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[O:4][C:5]=3[N:6]=[CH:7][N:8]=2)[CH2:13]1

Participants

8

Reactant 4

HCID 4875Potassium IodideHCID 81531DiisopropylethylamineHCID 107604Methyl 4-bromobutyrateHCID 58280221rac-5-Bromo-6-phenyl-4-(piperidin-3-yloxy)furo[2,3-d]pyrimidine

Product 1

HCID 58280260(+/-)-4-{3-[(5-Bromo-6-phenylfuro[2,3-d]pyrimidin-4-yl)oxy]piperidin-1-yl}butanoic acid methyl ester

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Heat a mixture of 550 mg (1.47 mmol) of rac-5-bromo-6-phenyl-4-(piperidin-3-yloxy)furo[2,3-d]-pyrimidine, 532 mg (2.94 mmol) of 4-bromobutyric acid methyl ester, 24.4 mg (0.147 mmol) of potassium iodide and 0.77 ml (4.41 mmol) of N,N-diisopropylethylamine in 1.5 ml of THF under reflux for 2 h. After cooling, dilute with dichloromethane and add to water. After phase separation, extract the aqueous phase with dichloromethane. Combine the organic phases, wash with satd. sodium hydrogencarbonate solution, dry over magnesium sulphate and concentrate under reduced pressure. From the residue, after purification by preparative RP-HPLC (eluent: acetonitrile/water), 780 mg of the target product are isolated, which are used without further purification.

Workup

  1. temperatureHeat
  2. temperatureunder reflux for 2 h
  3. temperatureAfter cooling
  4. customAfter phase separation
  5. extractionextract the aqueous phase with dichloromethane
  6. washwash with satd
  7. dry with materialsodium hydrogencarbonate solution, dry over magnesium sulphate
  8. concentrationconcentrate under reduced pressure
  9. customFrom the residue, after purification by preparative RP-HPLC (eluent: acetonitrile/water), 780 mg of the target product
  10. customare isolated
  11. customwhich are used without further purification

Sources & evidence

ORD record
ord-6b868b763b2a41bcb950ccf6fc4bf4c3
Source dataset
uspto-grants-2012_12
Patent number
US08324222B2

Reaction notes

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