2,6-Lutidine → {2-[5-(5-Amino-7-oxo-6,7-dihydro-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-4-hydroxy-tetrahydro-furan-2-yl]-vinyl}-phosphonic acid

HRID 2191016Notes

Reaction equation

HRID 2191016 reaction equation
[NH2:1][C:2]1[NH:3][C:4](=[O:35])[C:5]2[N:10]=[N:9][N:8]([CH:11]3[CH:15]([O:16]C(=O)C4C=CC=CC=4)[CH2:14][CH:13]([CH:25]=[CH:26][P:27]([O:32]CC)([O:29]CC)=[O:28])[O:12]3)[C:6]=2[N:7]=1.N1C(C)=CC=CC=1C.C[Si](Br)(C)C.[NH4+].[OH-].C([O-])(O)=O.[Na+]>CC#N>[NH2:1][C:2]1[NH:3][C:4](=[O:35])[C:5]2[N:10]=[N:9][N:8]([CH:11]3[O:12][CH:13]([CH:25]=[CH:26][P:27](=[O:28])([OH:29])[OH:32])[CH2:14][CH:15]3[OH:16])[C:6]=2[N:7]=1

Participants

7

Reactant 5

HCID 79372,6-LutidineHCID 14923Ammonium HydroxideHCID 76113BromotrimethylsilaneHCID 516892Sodium BicarbonateHCID 136381447Benzoic acid 2-(5-amino-7-oxo-6,7-dihydro-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-5-[2-(diethoxy-phosphoryl)-vinyl]-tetrahydro-furan-3-yl ester

Product 1

HCID 136381448{2-[5-(5-Amino-7-oxo-6,7-dihydro-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-4-hydroxy-tetrahydro-furan-2-yl]-vinyl}-phosphonic acidYield 82.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

Compound 10.1 (390 mg, 0.774 mmol) was dissolved in 15 mL CH3CN, treated with 2,6-lutidine (0.3 mL, 2.59 mmol) and TMSBr (1.5 mL, 11.4 mmol). The mixture was stirred for 2 h and coevaporated with CH3CN under reduced pressure. The residue was treated with NH4OH (10 mL) and stirred at 45° C. for 1.5 h. The mixture was treated with 500 mg NaHCO3 and concentrated down under reduced pressure. The residue was subjected to reverse phase HPLC eluting with 0-25% CH3CN in water to yield compound 10.2 (220 mg, 73% yield). 1H NMR (D2O) δ 2.28 (m, 1H), 2.45 (m, 1H), 4.90 (m, 2H), 5.8 (m, 1H), 6.15 (m, 1H). 31P NMR (D2O) d 18.77. LRMS (ESI) MH+ C10H13N6O6P requires 345.2. Found 345.0.

Workup

  1. stirringstirred at 45° C. for 1.5 h
  2. concentrationconcentrated down under reduced pressure
  3. washHPLC eluting with 0-25% CH3CN in water

Sources & evidence

ORD record
ord-f537c4ca07844606b44738faaee4b56f
Source dataset
uspto-grants-2012_12
Patent number
US08324179B2

Reaction notes

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