Chlorotrimethylsilane → N2-hexanoyl-9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine

HRID 1368691Notes

Reaction equation

HRID 1368691 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:30])[CH2:25][CH2:26][CH2:27][CH2:28][CH3:29].N12CCCN=C1CCCCC2>N1C=CC=CC=1.O.CO>[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:30])[CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]

Participants

8

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 67340Hexanoyl chlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 135398748Penciclovir

Product 1

HCID 136018077N2-hexanoyl-9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanineYield 14.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 1049PyridineSolvent

Procedure

To a suspension of 9-(4-hydroxy-3-hydroxymethylbut-1-yl)-guanine (0.25 g, 1.0 mmol) in pyridine (5 ml) was added chlorotrimethylsilane (0.32 ml, 2.5 mmol) and the mixture was stirred for 15 minutes. To this mixture was added hexanoyl chloride (0.18 ml, 1.3 mmol) and the mixture was stirred for 20 minutes. Methanol (2 ml) was then added and the mixture was stirred for a further 20 minutes. 1,8-Diazabicyclo[5.4.0]undec-7-ene (0.57 ml, 3.8 mmol) and water (0.5 ml) were added and the solvent was removed. The residue was purified by column chromatography on silica gel eluting with chloroform-methanol (4:1). Product containing fractions were pooled and the solvent removed. The residue was taken up in water and passed through C18-Sep-pak cartridges to afford N2-hexanoyl-9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine (50 mg, 14%), m.p. 86-88° C.; νmax (KBr) 3400, 2960, 2940, 1675, 1610, and 1560 cm−1; δH [(CD3)2SO] 0.88 (3H, t, J 6.7 Hz, CH3) 1.29 (4H, m, CH3(CH2)2), 1.46 (1H, m, 3′-H), 1.60 (2H, m, CH2CH2CO), 1.77 (2H, q, J 7.1 Hz, 2′-H), 2.46 (2H, t, J 7.4 Hz, CH2CO) 3.3-3.5 (4H, m, 2×4′-H), 4.13 (2H, t, J 7.4 Hz, 1′-H), 4.41 (2H, t, J 4.7 Hz, D2O exchangeable, 2×OH), 7.98 (1H, s, 8-H), 11.65 (1H, br, D2O exchangeable, NH), and 12.01 (1H, br, D2O exchangeable, NH); (Found: C, 53.64; H, 7.56; N, 18.95%; C16H25N5O4.0.5H2O requires: C, 53.32; H, 7.27; N, 19.43%).

Workup

  1. stirringthe mixture was stirred for 20 minutes
  2. stirringthe mixture was stirred for a further 20 minutes
  3. customthe solvent was removed
  4. customThe residue was purified by column chromatography on silica gel eluting with chloroform-methanol (4:1)
  5. additionProduct containing fractions
  6. customthe solvent removed

Sources & evidence

ORD record
ord-e788992d9dc84eb88a0f184ccd22d39a
Source dataset
uspto-grants-2003_06
Patent number
US06573378B1

Reaction notes

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