Formic Acid → 9-(1-Diethoxyphosphorylmethoxy-3-hydroxyprop-2-oxy)guanine

HRID 345078Notes

Reaction equation

HRID 345078 reaction equation
[Si]([O:8][CH2:9][CH:10]([O:22][N:23]1[CH:31]=[N:30][C:29]2[C:24]1=[N:25][C:26]([NH:33]C=O)=[N:27][C:28]=2Cl)[CH2:11][O:12][CH2:13][P:14]([O:19][CH2:20][CH3:21])([O:16][CH2:17][CH3:18])=[O:15])(C(C)(C)C)(C)C.C(O)=[O:37]>>[CH2:17]([O:16][P:14]([CH2:13][O:12][CH2:11][CH:10]([O:22][N:23]1[CH:31]=[N:30][C:29]2[C:28](=[O:37])[NH:27][C:26]([NH2:33])=[N:25][C:24]1=2)[CH2:9][OH:8])([O:19][CH2:20][CH3:21])=[O:15])[CH3:18]

Participants

3

Reactant 2

HCID 284Formic AcidHCID 545026429-(1-t-Butyldimethylsilyloxy-3-diethoxyphosphorylmethoxyprop-2-oxy)-6-chloro-2-formamidopurine

Product 1

HCID 1363411979-(1-Diethoxyphosphorylmethoxy-3-hydroxyprop-2-oxy)guanineYield 53%

Conditions

Temperature
20 °C

Procedure

A solution of 9-(1-t-butyldimethylsilyloxy-3-diethoxyphosphorylmethoxyprop-2-oxy)-6-chloro-2-formamidopurine (280 mg, 0.51 mmol) in 80% aqueous formic acid (5 ml) was stirred at 120° C. for 3 hours. The acid was evaporated, the residue dissolved in methanol (1 ml) and 0.88 ammonia (1 ml) and stirred for 1 hour at 20° C. After evaporation, the residue was dissolved in hot water (5 ml) and extracted with ether (3×5 ml). The aqueous solution was passed down a reverse-phase silica column eluting with up to 15% methanol affording 9-(1-diethoxyphosphorylmethoxy-3-hydroxyprop-2-oxy)guanine (105 mg, 53%) m.p. 238°-240° C. νmax (KBr) 3380, 1700, 1600, 1380, 1380, 1240, 1030 and 960 cm-1 ; δH [(CD3)2SO] 1.24(6H, t, J7.2 Hz, 2×(CH2CH3 ), 3.61(2H, t, J5.2 Hz, CH2OH), 3.81(2H, d, J4.7 Hz, CH2OCH2P), 3.89(2H. d, J8.0 Hz,CH2P), 4.04 (4H, m, 2×CH2CH3, 4.39(1H, t, J4.7 Hz,CHON), 5.06(1H, t, J6.0 Hz, D2O exchangeable, OH), 6.61(2H, br.s, D2O exchangeable, NH2), 7.86(1H, s, H-8), 10.67(1H, br.s, D2O exchangeable, NH); m/z (FAB+veIon), 392(MH+, 2%), 414(MNa+, 100%). Found: C,39.27; H,5.60; N,17.78%; C13H22N5O7P.0.3H2O requires C,39.36; H,5.74; N,17.66%.

Workup

  1. customThe acid was evaporated
  2. dissolutionthe residue dissolved in methanol (1 ml)
  3. customAfter evaporation
  4. dissolutionthe residue was dissolved in hot water (5 ml)
  5. extractionextracted with ether (3×5 ml)
  6. washeluting with up to 15% methanol

Sources & evidence

ORD record
ord-6211f10c892e416bab9bcc9f119c491a
Source dataset
uspto-grants-1991_10
Patent number
US05055458

Reaction notes

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