Water → 4-{[(3R)-1-Benzylpiperidin-3-yl]oxy}-5-(4-ethylphenyl)-6-iodofuro[2,3-d]pyrimidine

HRID 2189072Notes

Reaction equation

HRID 2189072 reaction equation
[H-].[Na+].[CH2:3]([N:10]1[CH2:15][CH2:14][CH2:13][C@@H:12]([OH:16])[CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl[C:18]1[C:19]2[C:26]([C:27]3[CH:32]=[CH:31][C:30]([CH2:33][CH3:34])=[CH:29][CH:28]=3)=[C:25]([I:35])[O:24][C:20]=2[N:21]=[CH:22][N:23]=1.O>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C>[CH2:3]([N:10]1[CH2:15][CH2:14][CH2:13][C@@H:12]([O:16][C:18]2[C:19]3[C:26]([C:27]4[CH:28]=[CH:29][C:30]([CH2:33][CH3:34])=[CH:31][CH:32]=4)=[C:25]([I:35])[O:24][C:20]=3[N:21]=[CH:22][N:23]=2)[CH2:11]1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

8

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 693761(R)-1-benzylpiperidin-3-olHCID 582802194-Chloro-5-(4-ethylphenyl)-6-iodofuro[2,3-d]pyrimidine

Product 1

HCID 582800744-{[(3R)-1-Benzylpiperidin-3-yl]oxy}-5-(4-ethylphenyl)-6-iodofuro[2,3-d]pyrimidine

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Add 106 mg (2.65 mmol) of sodium hydride (60% dispersion in mineral oil) to a solution of 483 mg (2.53 mmol) of (3R)-1-benzylpiperidin-3-ol [H. Tomori, Bull. Chem. Soc. Jpn. 69, 1, 207-216 (1996)] in 5 ml of THF. After stirring for ten minutes, add a solution of 1020 mg (70% purity, 1.86 mmol) of 4-chloro-5-(4-ethylphenyl)-6-iodofuro[2,3-d]pyrimidine in 5 ml of THF and 47 mg (0.13 mmol) of tetra-n-butylammonium iodide. Stir the reaction mixture at room temperature for five hours. After adding water and ethyl acetate, wash the removed organic phase with 1N hydrochloric acid and satd. sodium chloride solution and then concentrate under reduced pressure. Take up the residue in acetonitrile and purify by means of preparative RP-HPLC (gradient: water/acetonitrile). 266 mg (20% of theory) of the desired product are obtained.

Workup

  1. stirringStir the reaction mixture at room temperature for five hours
  2. washwash the removed organic phase with 1N hydrochloric acid
  3. concentrationsodium chloride solution and then concentrate under reduced pressure
  4. custompurify by means of preparative RP-HPLC (gradient: water/acetonitrile)

Sources & evidence

ORD record
ord-051ca7fee2b24bc99674c09a67ef4dc0
Source dataset
uspto-grants-2012_12
Patent number
US08324222B2

Reaction notes

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