Tetramethyl orthocarbonate → 2-Amino-9-(3-hydroxymethyl-4-methoxycarbonyloxybut-1-yl)purine

HRID 1655533

Reaction equation

HRID 1655533 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.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[C:30](OC)(OC)([O:33]C)[O:31][CH3:32].C(=O)(O)[O-].[Na+]>O1CCCC1.O>[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][O:15][C:30]([O:31][CH3:32])=[O:33])=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 74613Tetramethyl orthocarbonateHCID 1285176-DeoxypenciclovirHCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrate

Product 1

HCID 138831922-Amino-9-(3-hydroxymethyl-4-methoxycarbonyloxybut-1-yl)purine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 2-amino-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine (237 mg, 1.0 mmol) in dry tetrahydrofuran (3 ml) were added p-toluene-sulphonic acid monohydrate (0.21 g, 1.1 mmol) and tetramethyl orthocarbonate (0.53 ml, 4.0 mmol) and the mixture was stirred for 100 minutes. Water (0.8 ml) was added and after a further 15 minutes the solution was neutralised by addition of aqueous sodium bicarbonate. The solvent was removed and the residue was extracted with chloroform-methanol (3:1). The solvent was removed and the residue was purified by column chromatography on silica gel eluting with chloroform-methanol (10:1) to afford 2-amino-9-(3-hydroxymethyl-4-methoxycarbonyloxybut-1-yl)purine which was obtained as a white crystalline solid after trituration with ethyl acetate (65 mg, 22%), m.p. 129°-132°; νmax (KBr) 3440, 3220, 1745, 1650, 1615, and 1580 cm-1 ; &H [(CD3)2SO] 1.73 (1 H, m, 3'-H), 1.81 (2H, m, 2'-H), 3.41 (2H, t, J 5.1Hz, D2O exchange gives d, CH2OH) 3.68 (3H, s, CH3), 4.0-4.2 (4H, m, CH2OCO and 1'-H), 4.65 (1H, t, J 5.2Hz, D2O exchangeable, OH), 6.44 (2H, s, D2O exchangeable, 2-NH2), 8.06 (1H, s, 8-H), and 8.55 (1H, s, 6-H); (Observed M+, 295.1286, C12H17N5O4 requires 295.1280).

Workup

  1. customThe solvent was removed
  2. extractionthe residue was extracted with chloroform-methanol (3:1)
  3. customThe solvent was removed
  4. customthe residue was purified by column chromatography on silica gel eluting with chloroform-methanol (10:1)

Sources & evidence

ORD record
ord-da929662cd5147dc8a3a3e2c7e4c67ee
Source dataset
uspto-grants-1993_10
Patent number
US05250688

Linked notes

Loading…