Dioxolane-diacetate → HCID 178508933, compound

HRID 265621Notes

Reaction equation

HRID 265621 reaction equation
C([N:4](C(=O)C)[C:5]1[NH:6][C:7](=[O:14])[C:8]2[NH:9][CH:10]=[N:11][C:12]=2[N:13]=1)(=O)C.[O:18]1[CH2:22][CH2:21][O:20][C:19]1(CC([O-])=O)CC([O-])=O>>[CH:10]1[N:11]([CH2:19][O:18][CH2:22][CH2:21][OH:20])[C:12]2[N:13]=[C:5]([NH2:4])[N:6]=[C:7]([OH:14])[C:8]=2[N:9]=1

Participants

3

Reactant 2

HCID 19034566Dioxolane-diacetateHCID 136360183Diacetylguanine

Product 1

HCID 178508933HCID 178508933, compound

Procedure

On monitoring this reaction by thin layer chromatography, it was determined that the condensation of diacetyl guanine with dioxolane-diacetate in the presence of acidic catalyst produced N7 -isomer first, which was partially converted to N9 -isomers to reach an equilibrium in the ratio of 3/2 in favor of N9 -isomers. Under these condensation conditions, pure N7 - or N9 -acyclovir diacetate could be converted to give the same equilibrated mixture. This observation resulted in one of the embodiments of the improved process for the production of acyclovir of the present invention. When diacetyl quanine (4) almost disappeared during the condensation reaction, the reaction mixture was concentrated to dryness in vacuo, during which time the ratio of N9 /N7 -isomer continuously changed from approximately 3/2 to nearly one spot (N9 -isomer) as indicated by thin layer chromatography. The pure acyclovir diacetate (5) was obtained by simply washing with chloroform in good yield. It was surprising to learn that the ratio of N9 /N7 -isomers could be significantly manipulated in this manner.

Workup

  1. customOn monitoring this reaction by thin layer chromatography, it
  2. customproduced N7 -isomer first, which
  3. customUnder these condensation conditions, pure N7 -
  4. customto give the same equilibrated mixture

Sources & evidence

ORD record
ord-f154675034a243808c8a62e7fff3293d
Source dataset
uspto-grants-1997_07
Patent number
US05648489

Reaction notes

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