Pyridine → Famciclovir

HRID 1682105Notes

Reaction equation

HRID 1682105 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][CH2:12][CH:13]([CH2:16][OH:17])[CH2:14][OH:15])=[CH:4][N:3]=1.N1[CH:23]=[CH:22]C=CC=1.[C:24](OC(=O)C)(=[O:26])[CH3:25].C(Cl)(Cl)Cl.C[OH:36]>O1CCCC1.CN(C)C1C=CN=CC=1>[C:24]([O:15][CH2:14][CH:13]([CH2:16][O:17][C:22](=[O:36])[CH3:23])[CH2:12][CH2:11][N:8]1[CH:7]=[N:6][C:5]2[C:9]1=[N:10][C:2]([NH2:1])=[N:3][CH:4]=2)(=[O:26])[CH3:25]

Participants

7

Reactant 4

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 1285176-DeoxypenciclovirHCID 21584188Chloroform methanol

Product 1

HCID 3324Famciclovir

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 2-amino-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine (0.13 g, 0.55 mmol) in dry tetrahydrofuran (40 ml), stirred at room temperature under dry nitrogen were added pyridine (117 μl, 1.45 mmol) and 4-dimethylaminopyridine (5 mg, 41 μmol) followed by acetic anhydride (108 μl, 1.14 mmol). The mixture was stirred at room temperature for 5 h. giving a clear, colourless solution. T.1.c. [chloroform/methanol (9:1)] showed the major product to be the title compound, rf=0.40. Methanol (5 ml) was added, the mixture stirred for 5 mins. then evaporated to dryness. The residue was partitioned between water (5 ml) and chloroform (10 ml). The aqueous portion was extracted with chloroform (4×10 ml) then the combined organic portions dried over magnesium sulphate, filtered and evaporated to leave a pale yellow glassy material which was column chromatographed on silica (20 g) [eluant=chloroform/methanol (19:1)] to give the title compound (0.16 g, 91%) as a colourless viscous oil, which was crystallised from n-butanol (0.6 ml) to give colourless crystals (118 mg., 67%), m.p. 102° C.

Workup

  1. stirringThe mixture was stirred at room temperature for 5 h.
  2. customgiving a clear, colourless solution

Sources & evidence

ORD record
ord-40f53cedb8024e728c0c6e19d6cc598a
Source dataset
uspto-grants-1992_12
Patent number
US05175288

Reaction notes

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