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-((((4-azidobenzyl)oxy)carbonyl)amino)pentanoate

HRID 1482352Notes

Reaction equation

HRID 1482352 reaction equation
FC(F)(F)C(O)=O.[N:8]([C:11]1[CH:77]=[CH:76][C:14]([CH2:15][O:16][C:17]([NH:19][CH2:20][CH2:21][CH2:22][C@@H:23]([NH:68]C(OC(C)(C)C)=O)[C:24]([O:26][C@H:27]2[C@@H:31]([OH:32])[C@H:30]([N:33]3[CH:41]=[N:40][C:39]4[C:34]3=[N:35][CH:36]=[N:37][C:38]=4[NH2:42])[O:29][C@H:28]2[CH2:43][O:44][P:45]([O:48][C@H:49]2[CH2:53][C@H:52]([N:54]3[CH:59]=[CH:58][C:57]([NH2:60])=[N:56][C:55]3=[O:61])[O:51][C@@H:50]2[CH2:62][O:63][P:64]([OH:67])([OH:66])=[O:65])([OH:47])=[O:46])=[O:25])=[O:18])=[CH:13][CH:12]=1)=[N+:9]=[N-:10]>ClCCl>[NH2:68][C@H:23]([CH2:22][CH2:21][CH2:20][NH:19][C:17]([O:16][CH2:15][C:14]1[CH:13]=[CH:12][C:11]([N:8]=[N+:9]=[N-:10])=[CH:77][CH:76]=1)=[O:18])[C:24]([O:26][C@H:27]1[C@@H:31]([OH:32])[C@H:30]([N:33]2[CH:41]=[N:40][C:39]3[C:34]2=[N:35][CH:36]=[N:37][C:38]=3[NH2:42])[O:29][C@H:28]1[CH2:43][O:44][P:45]([O:48][C@H:49]1[CH2:53][C@H:52]([N:54]2[CH:59]=[CH:58][C:57]([NH2:60])=[N:56][C:55]2=[O:61])[O:51][C@@H:50]1[CH2:62][O:63][P:64]([OH:67])([OH:66])=[O:65])([OH:47])=[O:46])=[O:25]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 117736158(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-((((4-azidobenzyl)oxy)carbonyl)amino)-2-((tert-butoxycarbonyl)amino)pentanoate

Product 1

HCID 117736087(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-((((4-azidobenzyl)oxy)carbonyl)amino)pentanoateYield 21.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A 10% solution of trifluoroacetic acid in dichloromethane (0.4 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-((((4-azidobenzyl)oxy)carbonyl)amino)-2-((tert-butoxycarbonyl)amino)pentanoate (Compound tk59) (22.7 mg, 0.022 mmol) in dichloromethane (0.4 mL), and the mixture was stirred at room temperature for 20 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-((((4-azidobenzyl)oxy)carbonyl)amino)pentanoate (Orn(Acbz)-pdCpA) (Compound tk60) (4.3 mg, 21%).

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-10e15e810ace4bdf96886c9edbfb83a0
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

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