Triethyl Phosphate → Triethylammonium 2-(6-cyano-1-hexyn-1-yl)adenosine 5'-monophosphate

HRID 586122Notes

Reaction equation

HRID 586122 reaction equation
[C:1]([CH2:3][CH2:4][CH2:5][CH2:6][C:7]#[C:8][C:9]1[N:10]=[C:11]([NH2:27])[C:12]2[N:13]=[CH:14][N:15]([C:25]=2[N:26]=1)[C@@H:16]1[O:24][C@H:21]([CH2:22][OH:23])[C@@H:19]([OH:20])[C@H:17]1[OH:18])#[N:2].P(Cl)(Cl)(Cl)=O.[OH-].[Na+].[P:35](O[CH2:44][CH3:45])([O:40]CC)([O:37][CH2:38]C)=[O:36]>>[P:35]([O:23][CH2:22][C@H:21]1[O:24][C@@H:16]([N:15]2[C:25]3[N:26]=[C:9]([C:8]#[C:7][CH2:6][CH2:5][CH2:4][CH2:3][C:1]#[N:2])[N:10]=[C:11]([NH2:27])[C:12]=3[N:13]=[CH:14]2)[C@H:17]([OH:18])[C@@H:19]1[OH:20])([O-:40])([O-:37])=[O:36].[CH2:9]([NH+:10]([CH2:44][CH3:45])[CH2:11][CH3:12])[CH3:8].[CH2:16]([NH+:15]([CH2:25][CH3:12])[CH2:14][CH3:38])[CH3:17]

Participants

5

Reactant 4

HCID 6535Triethyl PhosphateHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 112109712-(6-Cyano-1-hexyn-1-yl)adenosine

Product 1

HCID 69595338Triethylammonium 2-(6-cyano-1-hexyn-1-yl)adenosine 5'-monophosphate

Procedure

Under argon, A 2-(6-cyano-1-hexyn-1-yl)adenosine (2.41 g) was dissolved in triethyl phosphate (15 mL), and, under ice-cooling conditions, phosphorous oxychloride (25.2 mL, 3.9 eq.) was added thereto, followed by stirring at the same temperature for 5 hours. The reaction mixture was added dropwise to a 10% sodium hydroxide solution (300 mL), and the resultant mixture was washed with ether. The aqueous layer was separated and water was removed under reduced pressure, and the residue was purified by C18 silica gel column chromatography (0.1M triethylammonium acetate buffer:acetonitrile=100:0 to 60:40). The thus-obtained fraction was concentrated, and the concentrate was subjected to C18 silica gel column chromatography (water:acetonitrile=100:0 to 60:40), to thereby remove the triethylammonium acetate buffer. The residue was freeze-dried, to thereby yield 1.14 g of the above-titled compound as a colorless amorphous substance.

Workup

  1. additionwas added
  2. washthe resultant mixture was washed with ether
  3. customThe aqueous layer was separated
  4. customwater was removed under reduced pressure
  5. customthe residue was purified by C18 silica gel column chromatography (0.1M triethylammonium acetate buffer:acetonitrile=100:0 to 60:40)
  6. concentrationThe thus-obtained fraction was concentrated
  7. customto thereby remove the triethylammonium acetate buffer
  8. customThe residue was freeze-dried

Sources & evidence

ORD record
ord-f410a939816a4c57bc75ff1609cc1cf6
Source dataset
uspto-grants-2005_08
Patent number
US06936596B2

Reaction notes

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