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-azido-4-(isopropyldisulfanyl)pentanoate

HRID 1482312Notes

Reaction equation

HRID 1482312 reaction equation
FC(F)(F)C(O)=O.[N:8]([CH2:11][CH:12]([S:67][S:68][CH:69]([CH3:71])[CH3:70])[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][CH:12]([S:67][S:68][CH:69]([CH3:71])[CH3:70])[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 117736422(2S)-(2R,3S,4R,5R)-2-((((((2R,3S,5R)-5-(4-amino-2-oxopyrimidine-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)-4-(isopropyldisulfanyl)pentanoate2×

Product 1

HCID 117736389(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-azido-4-(isopropyldisulfanyl)pentanoateYield 87%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (0.1 mL) was added to a solution of (2S)-(2R,3S,4R,5R)-2-((((((2R,3S,5R)-5-(4-amino-2-oxopyrimidine-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)-4-(isopropyldisulfanyl)pentanoate (Compound 46) (27.7 mg, 28 μmol) in dichloromethane (0.4 mL), and the mixture was stirred for 35 minutes at room temperature. 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-azido-4-(isopropyldisulfanyl)pentanoate (Orn(N3) (4-SSiPr)-pdCpA) (Compound 47) (21.5 mg, 86%).

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-5741df30ea224dfcbb23bc0c86d4b189
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

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