Trifluoroacetic acid → (2R,3S,4R,5R)-2-((((2R,3S,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-2-(phosphonooxymethyl)tetrahydrofuran-3-yloxy)(hydroxy)phosphoryloxy)methyl)-5-(6-amino-9H-purin-9-yl)-4-hydroxytetrahydrofuran-3-yl 2-hydroxyacetate

HRID 1482299Notes

Reaction equation

HRID 1482299 reaction equation
FC(F)(F)C(O)=O.[Si]([O:15][CH2:16][C:17]([O:19][C@H:20]1[C@@H:24]([OH:25])[C@H:23]([N:26]2[CH:34]=[N:33][C:32]3[C:27]2=[N:28][CH:29]=[N:30][C:31]=3[NH2:35])[O:22][C@@H:21]1[CH2:36][O:37][P:38]([O:41][C@H:42]1[CH2:46][C@H:45]([N:47]2[CH:52]=[CH:51][C:50]([NH2:53])=[N:49][C:48]2=[O:54])[O:44][C@@H:43]1[CH2:55][O:56][P:57]([OH:60])([OH:59])=[O:58])([OH:40])=[O:39])=[O:18])(C(C)(C)C)(C)C>ClCCl>[OH:15][CH2:16][C:17]([O:19][C@H:20]1[C@@H:24]([OH:25])[C@H:23]([N:26]2[CH:34]=[N:33][C:32]3[C:27]2=[N:28][CH:29]=[N:30][C:31]=3[NH2:35])[O:22][C@@H:21]1[CH2:36][O:37][P:38]([O:41][C@H:42]1[CH2:46][C@H:45]([N:47]2[CH:52]=[CH:51][C:50]([NH2:53])=[N:49][C:48]2=[O:54])[O:44][C@@H:43]1[CH2:55][O:56][P:57]([OH:59])([OH:60])=[O:58])([OH:40])=[O:39])=[O:18]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 131736701(2R,3S,4R,5R)-2-((((2R,3S,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-2-(phosphonooxymethyl)tetrahydrofuran-3-yloxy)(hydroxy)phosphoryloxy)methyl)-5-(6-amino-9H-purin-9-yl)-4-hydroxytetrahydrofuran-3-yl 2-(tert-butyldimethylsilyloxy)acetate2×

Product 1

HCID 89668653(2R,3S,4R,5R)-2-((((2R,3S,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-2-(phosphonooxymethyl)tetrahydrofuran-3-yloxy)(hydroxy)phosphoryloxy)methyl)-5-(6-amino-9H-purin-9-yl)-4-hydroxytetrahydrofuran-3-yl 2-hydroxyacetateYield 23.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (2 ml) was added to a solution of (2R,3S,4R,5R)-2-((((2R,3S,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-2-(phosphonooxymethyl)tetrahydrofuran-3-yloxy)(hydroxy)phosphoryloxy)methyl)-5-(6-amino-9H-purin-9-yl)-4-hydroxytetrahydrofuran-3-yl 2-(tert-butyldimethylsilyloxy)acetate (Compound 22) (70.0 mg, 87 μmol) in dichloromethane (2 ml) at room temperature, and the mixture was stirred at the same temperature for 30 minutes. Following concentration under reduced pressure, the resulting residue was purified by reverse-phase silica gel column chromatography (0.1% aqueous formic acid solution/0.1% formic acid-acetonitrile solution) to afford (2R,3S,4R,5R)-2-((((2R,3S,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-2-(phosphonooxymethyl)tetrahydrofuran-3-yloxy)(hydroxy)phosphoryloxy)methyl)-5-(6-amino-9H-purin-9-yl)-4-hydroxytetrahydrofuran-3-yl 2-hydroxyacetate (HOGly-pdCpA) (Compound 20) (14.0 mg, 23%).

Workup

  1. concentrationconcentration under reduced pressure
  2. customthe resulting residue was purified by reverse-phase silica gel column chromatography (0.1% aqueous formic acid solution/0.1% formic acid-acetonitrile solution)

Sources & evidence

ORD record
ord-1b8867c5f91f4caa9f26cf30ceed99e1
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

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