Hydrochloric Acid → (E)-9-[2-hydroxymethyl-4-(diisopropoxyphosphoryl)but-3-enyl]adenine

HRID 1708105Notes

Reaction equation

HRID 1708105 reaction equation
[N:1]([C:4]1[N:12]=[CH:11][N:10]=[C:9]2[C:5]=1[N:6]=[CH:7][N:8]2[CH2:13][CH:14]([CH2:27][O:28][Si](C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1)/[CH:15]=[CH:16]/[P:17]([O:23][CH:24]([CH3:26])[CH3:25])([O:19][CH:20]([CH3:22])[CH3:21])=[O:18])=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl>O1CCCC1>[CH:20]([O:19][P:17](/[CH:16]=[CH:15]/[CH:14]([CH2:27][OH:28])[CH2:13][N:8]1[CH:7]=[N:6][C:5]2[C:9]1=[N:10][CH:11]=[N:12][C:4]=2[NH2:1])([O:23][CH:24]([CH3:25])[CH3:26])=[O:18])([CH3:21])[CH3:22]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 10416777(E)-6-azido-9-[2-(t-butyldiphenylsilyloxy)methyl-4-(diisopropoxyphosphoryl)but-3-enyl]purine

Product 1

HCID 10317795(E)-9-[2-hydroxymethyl-4-(diisopropoxyphosphoryl)but-3-enyl]adenineYield 65.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

* Mixture of Azido and Tetrazolo Tautomers c) A solution of (E)-6-azido-9-[2-(t-butyldiphenylsilyloxy)methyl-4-(diisopropoxyphosphoryl)but-3-enyl]purine (320 mg, 494 μmol) and triphenylphosphine (194 mg, 741 μmol) in tetrahydrofuran (15 ml) was stirred at room temperature for 21 h. The solution was heated to 70° C. and 5M hydrochloric acid (258 μl, 1.29 mmol) added. After 2 h, the solvent was removed and the residue was dissolved in 3% methanolic hydrogen chloride (10 ml) and the solution stirred at room temperature for 2 h. The solvent was removed, the residue dissolved in water and the solution neutralised by addition of aqueous sodium bicarbonate solution. The solution was evaporated to dryness and the residue purified by column chromatography on silica gel eluting with dichloromethane-methanol (9:1, 6:1) to give the title compound as a white solid (124 mg, 63%), m.p. 130° C.; λmax (EtOH) 261 (13,074)nm; υmax (KBr) 3325, 2980, 1645, 1600, 1475, 1420, 1240 and 990 cm-1 ; δH [(CD3)2SO] 1.10 (12H, m, CH3), 3.07 (1H, m, CH), 3.50 (2H, t, J 5Hz, CH2O), 4.10 (1H, m, CH(CH3)2)), 4.27 (3H, m, CH2N and CH(CH3 )2), 4.99 (1H, t, J 5Hz, D2O exchangeable, OH), 5.59 (1H, dd, J 17 Hz and 21 Hz, PCH=CH), 6.52 (1H, ddd, J 8 Hz, 17 Hz and 22 Hz, PCH=CH), 7.16 (2H, br.s, D2O exchangeable, NH2), 8.07 (1H, s, H-2/H-8), 8.12 (1H, s, H-2/H-8); CIMS 384 (MH+) (Found: C, 48.92; H, 6.90; N, 17.58%. C16H26N5O4P.0.5 H2O requires C, 48.97; H, 6.94; N, 17.85%).

Workup

  1. temperatureThe solution was heated to 70° C.
  2. waitAfter 2 h
  3. customthe solvent was removed
  4. dissolutionthe residue was dissolved in 3% methanolic hydrogen chloride (10 ml)
  5. stirringthe solution stirred at room temperature for 2 h
  6. customThe solvent was removed
  7. dissolutionthe residue dissolved in water
  8. additionthe solution neutralised by addition of aqueous sodium bicarbonate solution
  9. customThe solution was evaporated to dryness
  10. customthe residue purified by column chromatography on silica gel eluting with dichloromethane-methanol (9:1, 6:1)

Sources & evidence

ORD record
ord-055f2760ce884b1b88155f8afd052a8f
Source dataset
uspto-grants-1994_10
Patent number
US05356886

Reaction notes

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