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-(tert-butyldisulfanyl)pentanoate

HRID 1482310Notes

Reaction equation

HRID 1482310 reaction equation
[N:1]([CH2:4][CH:5]([S:60][S:61][C:62]([CH3:65])([CH3:64])[CH3:63])[CH2:6][C@@H:7]([NH:52]C(OC(C)(C)C)=O)[C:8]([O:10][C@H:11]1[C@@H:15]([OH:16])[C@H:14]([N:17]2[CH:25]=[N:24][C:23]3[C:18]2=[N:19][CH:20]=[N:21][C:22]=3[NH2:26])[O:13][C@H:12]1[CH2:27][O:28][P:29]([O:32][C@H:33]1[CH2:37][C@H:36]([N:38]2[CH:43]=[CH:42][C:41]([NH2:44])=[N:40][C:39]2=[O:45])[O:35][C@@H:34]1[CH2:46][O:47][P:48]([OH:51])([OH:50])=[O:49])([OH:31])=[O:30])=[O:9])=[N+:2]=[N-:3].FC(F)(F)C(O)=O>ClCCl>[NH2:52][C@H:7]([CH2:6][CH:5]([S:60][S:61][C:62]([CH3:65])([CH3:64])[CH3:63])[CH2:4][N:1]=[N+:2]=[N-:3])[C:8]([O:10][C@H:11]1[C@@H:15]([OH:16])[C@H:14]([N:17]2[CH:25]=[N:24][C:23]3[C:18]2=[N:19][CH:20]=[N:21][C:22]=3[NH2:26])[O:13][C@H:12]1[CH2:27][O:28][P:29]([O:32][C@H:33]1[CH2:37][C@H:36]([N:38]2[CH:43]=[CH:42][C:41]([NH2:44])=[N:40][C:39]2=[O:45])[O:35][C@@H:34]1[CH2:46][O:47][P:48]([OH:51])([OH:50])=[O:49])([OH:31])=[O:30])=[O:9]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 117735900(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)-4-(tert-butyldisulfanyl)pentanoate2×

Product 1

HCID 117736222(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-(tert-butyldisulfanyl)pentanoateYield 50.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The aforementioned crude product 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-azide-2-((tert-butoxycarbonyl)amino)-4-(tert-butyldisulfanyl)pentanoate (Compound 42) (53 mg) was suspended by adding dichloromethane (2 ml) thereto, after which trifluoroacetic acid (0.5 mL) was added 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 (0.05% 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-(tert-butyldisulfanyl)pentanoate (Orn(N3) (4-SStBu)-pdCpA) (Compound 43) (24 mg, 31% in two steps).

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-0b5dda325d914faead6956bd89d9629d
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

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