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-4-((S)-thiazolidin-5-yl)butanoate

HRID 1482319Notes

Reaction equation

HRID 1482319 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C:9]1[CH:14]=[CH:13][N:12]([C@@H:15]2[O:19][C@H:18]([CH2:20][O:21][P:22]([OH:25])([OH:24])=[O:23])[C@@H:17]([O:26][P:27]([O:30][CH2:31][C@@H:32]3[C@@H:36]([O:37][C:38](=[O:62])[C@@H:39]([NH:54]C(OC(C)(C)C)=O)[CH2:40][CH2:41][C@@H:42]4[S:46][CH2:45][N:44](C(OC(C)(C)C)=O)[CH2:43]4)[C@@H:35]([OH:63])[C@H:34]([N:64]4[CH:72]=[N:71][C:70]5[C:65]4=[N:66][CH:67]=[N:68][C:69]=5[NH2:73])[O:33]3)([OH:29])=[O:28])[CH2:16]2)[C:11](=[O:74])[N:10]=1>ClCCl>[NH2:54][C@H:39]([CH2:40][CH2:41][C@@H:42]1[S:46][CH2:45][NH:44][CH2:43]1)[C:38]([O:37][C@H:36]1[C@@H:35]([OH:63])[C@H:34]([N:64]2[CH:72]=[N:71][C:70]3[C:65]2=[N:66][CH:67]=[N:68][C:69]=3[NH2:73])[O:33][C@H:32]1[CH2:31][O:30][P:27]([O:26][C@H:17]1[CH2:16][C@H:15]([N:12]2[CH:13]=[CH:14][C:9]([NH2:8])=[N:10][C:11]2=[O:74])[O:19][C@@H:18]1[CH2:20][O:21][P:22]([OH:24])([OH:25])=[O:23])([OH:29])=[O:28])=[O:62]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 89668710(5S)-tert-butyl 5-((3S)-4-(((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)Oxy)-3-((tert-butoxycarbonyl)amino)-4-oxobutyl)thiazolidine-3-carboxylate

Product 1

HCID 117736364(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-4-((S)-thiazolidin-5-yl)butanoateYield 155.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A 10% solution of trifluoroacetic acid in dichloromethane (0.16 mL) was added to a solution of (5S)-tert-butyl 5-((3S)-4-(((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)Oxy)-3-((tert-butoxycarbonyl)amino)-4-oxobutyl)thiazolidine-3-carboxylate (Compound tk4) (8.5 mg, 8.43 μmol) in dichloromethane (0.2 mL), and the mixture was stirred at room temperature for 1.25 hours. Following concentration under reduced pressure, (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-4-((S)-thiazolidin-5-yl)butanoate (Ala(Tzm)-pdCpA) (Compound tk5) (10.6 mg, quant.) was obtained.

Workup

  1. concentrationconcentration under reduced pressure

Sources & evidence

ORD record
ord-c0613814d1c948d2a2b9fa18bc547364
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

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