Methanol → N2-Acetyl-9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine

HRID 1368690Notes

Reaction equation

HRID 1368690 reaction equation
[OH:1][CH2:2][CH:3]([CH2:17][OH:18])[CH2:4][CH2:5][N:6]1[CH:14]=[N:13][C:12]2[C:11](=[O:15])[NH:10][C:9]([NH2:16])=[N:8][C:7]1=2.Cl[Si](C)(C)C.[C:24](Cl)(=[O:26])[CH3:25].CO>N1C=CC=CC=1>[C:24]([NH:16][C:9]1[NH:10][C:11](=[O:15])[C:12]2[N:13]=[CH:14][N:6]([CH2:5][CH2:4][CH:3]([CH2:17][OH:18])[CH2:2][OH:1])[C:7]=2[N:8]=1)(=[O:26])[CH3:25]

Participants

6

Reactant 4

HCID 887MethanolHCID 6367Acetyl chlorideHCID 6397ChlorotrimethylsilaneHCID 135398748Penciclovir

Product 1

HCID 136077201N2-Acetyl-9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a suspension of 9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine (0.23 g, 0.9 mmol) in pyridine (3 ml) was added chlorotrimethylsilane (0.25 ml, 2.0 mmol) and the mixture was stirred for 15 minutes. To this mixture was added acetyl chloride (0.085 ml, 1.2 mmol) and the mixture was stirred for 30 minutes. Methanol (2 ml) was the added and the mixture was stirred for a further 30 minutes. The solvent was removed and the residue purified by column chromatography on silica gel eluting with chloroform-methanol mixtures (4:1, 5:2) to give the title compound as its hydrochloride salt. This was dissolved in methanol and stirred with potassium carbonate. The solution was filtered and the solvent removed. The residue was taken up in water and passed through C18-Sep-pak cartridges. Fractions containing product were pooled and the solvent removed to afford N2-acetyl-9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine (0.11 g, 41%), m.p. 143-146° C.; λmax (H2O) 260 (15,100) nm; νmax (KBr) 3420, 3200, 2940, 1685, 1615, and 1560 cm−1; δH [(CD3)2SO] 1.46 (1H, m, 3′-H), 1.77 (2H, q, J 7.1 Hz, 2′-H), 2.18 (3H, s, CH3), 3.3-3.5 (4H, m, 2×4′-H), 4.13 (2H, t, J 7.4 Hz, 1′-H), 4.42 (2H, br.t, J 5 Hz, D2O exchangeable, 2×OH), 7.98 (1H, s, 8-H), and 11.83 (2H, br, D2O exchangeable, 1-H and 2-NH).

Workup

  1. stirringthe mixture was stirred for 30 minutes
  2. additionadded
  3. stirringthe mixture was stirred for a further 30 minutes
  4. customThe solvent was removed
  5. customthe residue purified by column chromatography on silica gel eluting with chloroform-methanol mixtures (4:1, 5:2)

Sources & evidence

ORD record
ord-f370711c4aeb451284fe10d73fe3aafc
Source dataset
uspto-grants-2003_06
Patent number
US06573378B1

Reaction notes

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