Bromotrimethylsilane → [(E)-4-(2,6-diaminopurin-9-yl)but-1-enyl]phosphonic acid

HRID 1708097Notes

Reaction equation

HRID 1708097 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]=[CH:14]/[P:15]([O:21]C(C)C)([O:17]C(C)C)=[O:16])=[C:4]([NH2:25])[N:3]=1.Br[Si](C)(C)C>ClCCl.CN(C)C=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]=[CH:14]/[P:15]([OH:21])([OH:17])=[O:16])=[C:4]([NH2:25])[N:3]=1

Participants

5

Reactant 2

HCID 76113Bromotrimethylsilane2×HCID 11726511(E)-2,6-diamino-9-[4-(diisopropoxy-phosphoryl)but-3-enyl]purine

Product 1

HCID 6474330[(E)-4-(2,6-diaminopurin-9-yl)but-1-enyl]phosphonic acidYield 27%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (E)-2,6-diamino-9-[4-(diisopropoxy-phosphoryl)but-3-enyl]purine (144mg, 391 μmol) in dichloromethane (10 ml) was added bromotrimethylsilane (1.20 g, 7.82 mmol) and the mixture stirred at room temperature under dry nitrogen for 18 hr. The resulting white suspension was evaporated to dryness and the residue azeotroped with methanol (×6). The residue was purified by column chromatography on reverse phase silica gel eluting with water to give a product which n.m.r. analysis showed to be the monoester. To a suspension of the monoester (approx. 306 μmol) in dry N,N-dimethylformamide (10 ml) was added bromotrimethylsilane (1.16 g, 7.58 mmol) and the resulting solution was stirred at room temperature under dry nitrogen for 18 hr. The solution was evaporated to dryness and the residue azeotroped with methanol (×3) then acetone-water (1:1) (×3). The residue was purified by column chromatography on reverse phase silica gel eluting with water to give (E)-2,6-diamino-9-(4-phosphonobut-3 -enyl)purine as a white solid (30 mg, 27%), m.p. >325° C.; λmax (MeOH) 256 (6,570) and 285 (6,490)nm; υmax (KBr) 3410, 1710, 1670, 1630, 1590, 1420, 1220 and 135 cm-1 ; δH [(CD3)2SO+one drop NH4OH solution] 2.50 (2H, m, CH2) 4.05 (2H, t, J 7 Hz, CH2N), 5.70 (1H, pseudo-t, J 17 Hz, PCH=CH), 5.81 (2H, s, NH2), 6.10 (1H, pseudo-tt, J 7 Hz and 20 Hz, PCH=CH), 6.69 (2H, s, NH2) , 7.76 (1H, s, H-8); FABMS thioglycerol) 285 (MH+).

Workup

  1. customThe resulting white suspension was evaporated to dryness
  2. customthe residue azeotroped with methanol (×6)
  3. customThe residue was purified by column chromatography on reverse phase silica gel eluting with water
  4. customto give a product which n.m.r
  5. stirringthe resulting solution was stirred at room temperature under dry nitrogen for 18 hr
  6. customThe solution was evaporated to dryness
  7. customthe residue azeotroped with methanol (×3)
  8. customThe residue was purified by column chromatography on reverse phase silica gel eluting with water

Sources & evidence

ORD record
ord-40b09fd4c4a54e7c8f36da1c202015b1
Source dataset
uspto-grants-1994_10
Patent number
US05356886

Reaction notes

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