Trifluoroacetic acid → (2S)-(2R,3S,4R,5R)-2-((((((2R,3S,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-2-((phosphonooxy)methyl)tetrahydrofuran-3-yl)oxy)(hydroxy)phosphoryl)oxy)methyl)-5-(6-amino-9H-purin-9-yl)-4-hydroxytetrahydrofuran-3-yl 2-amino-5-azidopentanoate

HRID 1482363Notes

Reaction equation

HRID 1482363 reaction equation
FC(F)(F)C(O)=O.[N:8]([CH2:11][CH2:12][CH2:13][C@@H:14]([NH:59]C(OC(C)(C)C)=O)[C:15]([O:17][C@H:18]1[C@@H:22]([OH:23])[C@H:21]([N:24]2[CH:32]=[N:31][C:30]3[C:25]2=[N:26][CH:27]=[N:28][C:29]=3[NH2:33])[O:20][C@H:19]1[CH2:34][O:35][P:36]([O:39][C@H:40]1[CH2:44][C@H:43]([N:45]2[CH:50]=[CH:49][C:48]([NH2:51])=[N:47][C:46]2=[O:52])[O:42][C@@H:41]1[CH2:53][O:54][P:55]([OH:58])([OH:57])=[O:56])([OH:38])=[O:37])=[O:16])=[N+:9]=[N-:10]>ClCCl>[NH2:59][C@H:14]([CH2:13][CH2:12][CH2:11][N:8]=[N+:9]=[N-:10])[C:15]([O:17][C@H:18]1[C@@H:22]([OH:23])[C@H:21]([N:24]2[CH:32]=[N:31][C:30]3[C:25]2=[N:26][CH:27]=[N:28][C:29]=3[NH2:33])[O:20][C@H:19]1[CH2:34][O:35][P:36]([O:39][C@H:40]1[CH2:44][C@H:43]([N:45]2[CH:50]=[CH:49][C:48]([NH2:51])=[N:47][C:46]2=[O:52])[O:42][C@@H:41]1[CH2:53][O:54][P:55]([OH:58])([OH:57])=[O:56])([OH:38])=[O:37])=[O:16]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 117736240(2S)-(2R,3S,4R,5R)-2-((((((2R,3S,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-2-((phosphonooxy)methyl)tetrahydrofuran-3-yl)oxy)(hydroxy)phosphoryl)oxy)methyl)-5-(6-amino-9H-purin-9-yl)-4-hydroxytetrahydrofuran-3-yl 5-azido-2-((tert-butoxycarbonyl)amino)pentanoate

Product 1

HCID 117736412(2S)-(2R,3S,4R,5R)-2-((((((2R,3S,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-2-((phosphonooxy)methyl)tetrahydrofuran-3-yl)oxy)(hydroxy)phosphoryl)oxy)methyl)-5-(6-amino-9H-purin-9-yl)-4-hydroxytetrahydrofuran-3-yl 2-amino-5-azidopentanoateYield 87%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (0.09 mL) was added to a solution of (2S)-(2R,3S,4R,5R)-2-((((((2R,3S,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-2-((phosphonooxy)methyl)tetrahydrofuran-3-yl)oxy)(hydroxy)phosphoryl)oxy)methyl)-5-(6-amino-9H-purin-9-yl)-4-hydroxytetrahydrofuran-3-yl 5-azido-2-((tert-butoxycarbonyl)amino)pentanoate (Compound tk71) (24.5 mg, 0.028 mmol) in dichloromethane (1 mL), and the mixture was stirred at room temperature for 25 minutes. Following concentration under reduced pressure, the resulting residue was purified by reverse-phase silica gel column chromatography (0.05% aqueous trifluoroacetic acid solution/0.05% trifluoroacetic acid-acetonitrile solution) to afford (2S)-(2R,3S,4R,5R)-2-((((((2R,3S,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-2-((phosphonooxy)methyl)tetrahydrofuran-3-yl)oxy)(hydroxy)phosphoryl)oxy)methyl)-5-(6-amino-9H-purin-9-yl)-4-hydroxytetrahydrofuran-3-yl 2-amino-5-azidopentanoate (Orn(N3)-pdCpA) (Compound tk72) (18.8 mg, 87%).

Workup

  1. concentrationconcentration under reduced pressure
  2. customthe resulting residue was purified by reverse-phase silica gel column chromatography (0.05% aqueous trifluoroacetic acid solution/0.05% trifluoroacetic acid-acetonitrile solution)

Sources & evidence

ORD record
ord-11e92595e4694f1ab55437ed8b1d8b22
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

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