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-6-azidohexanoate

HRID 1482345Notes

Reaction equation

HRID 1482345 reaction equation
FC(F)(F)C(O)=O.[N:8]([CH2:11][CH2:12][CH2:13][CH2:14][C@@H:15]([NH:60]C(OC(C)(C)C)=O)[C:16]([O:18][C@H:19]1[C@@H:23]([OH:24])[C@H:22]([N:25]2[CH:33]=[N:32][C:31]3[C:26]2=[N:27][CH:28]=[N:29][C:30]=3[NH2:34])[O:21][C@H:20]1[CH2:35][O:36][P:37]([O:40][C@H:41]1[CH2:45][C@H:44]([N:46]2[CH:51]=[CH:50][C:49]([NH2:52])=[N:48][C:47]2=[O:53])[O:43][C@@H:42]1[CH2:54][O:55][P:56]([OH:59])([OH:58])=[O:57])([OH:39])=[O:38])=[O:17])=[N+:9]=[N-:10]>ClCCl>[NH2:60][C@H:15]([CH2:14][CH2:13][CH2:12][CH2:11][N:8]=[N+:9]=[N-:10])[C:16]([O:18][C@H:19]1[C@@H:23]([OH:24])[C@H:22]([N:25]2[CH:33]=[N:32][C:31]3[C:26]2=[N:27][CH:28]=[N:29][C:30]=3[NH2:34])[O:21][C@H:20]1[CH2:35][O:36][P:37]([O:40][C@H:41]1[CH2:45][C@H:44]([N:46]2[CH:51]=[CH:50][C:49]([NH2:52])=[N:48][C:47]2=[O:53])[O:43][C@@H:42]1[CH2:54][O:55][P:56]([OH:59])([OH:58])=[O:57])([OH:39])=[O:38])=[O:17]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 117736203(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 6-azido-2-((tert-butoxycarbonyl)amino)hexanoate

Product 1

HCID 117736253(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-6-azidohexanoateYield 72.2%

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-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 6-azido-2-((tert-butoxycarbonyl)amino)hexanoate (Compound tk50) (30.2 mg, 0.034 mmol) in dichloromethane (1.5 mL), and the mixture was stirred at room 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-6-azidohexanoate (Lys(N3)-pdCpA) (Compound tk51) (19.4 mg, 72%).

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-1c815aa371e94d19b7762ff1c84f7b62
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

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