HCID 89668704, compound → HCID 117735646, compound

HRID 1482326Notes

Reaction equation

HRID 1482326 reaction equation
C([N+](CCCC)(CCCC)CCCC)CCC.[P:18]([O:22][CH2:23][C@@H:24]1[C@@H:28]([O:29][P:30]([O:33][CH2:34][C@@H:35]2[C@@H:39]([OH:40])[C@@H:38]([OH:41])[C@H:37]([N:42]3[CH:50]=[N:49][C:48]4[C:43]3=[N:44][CH:45]=[N:46][C:47]=4[NH2:51])[O:36]2)([OH:32])=[O:31])[CH2:27][C@H:26]([N:52]2[CH:57]=[CH:56][C:55]([NH2:58])=[N:54][C:53]2=[O:59])[O:25]1)([OH:21])([OH:20])=[O:19].[N:60]([C:63]1[CH:95]=[CH:94][CH:93]=[CH:92][C:64]=1[CH2:65][O:66][C:67]([NH:69][CH2:70][C@@H:71]([S:89][S:90][CH3:91])[CH2:72][CH2:73][C@H:74]([NH:81][C:82]([O:84][C:85]([CH3:88])([CH3:87])[CH3:86])=[O:83])[C:75](OCC#N)=[O:76])=[O:68])=[N+:61]=[N-:62]>C(#N)C>[N:60]([C:63]1[CH:95]=[CH:94][CH:93]=[CH:92][C:64]=1[CH2:65][O:66][C:67]([NH:69][CH2:70][C@H:71]([S:89][S:90][CH3:91])[CH2:72][CH2:73][C@@H:74]([NH:81][C:82]([O:84][C:85]([CH3:88])([CH3:87])[CH3:86])=[O:83])[C:75]([O:40][C@H:39]1[C@@H:38]([OH:41])[C@@H:37]([N:42]2[CH:50]=[N:49][C:48]3[C:43]2=[N:44][CH:45]=[N:46][C:47]=3[NH2:51])[O:36][C@H:35]1[CH2:34][O:33][P:30]([O:29][C@H:28]1[CH2:27][C@H:26]([N:52]2[CH:57]=[CH:56][C:55]([NH2:58])=[N:54][C:53]2=[O:59])[O:25][C@@H:24]1[CH2:23][O:22][P:18]([OH:21])([OH:20])=[O:19])([OH:32])=[O:31])=[O:76])=[O:68])=[N+:61]=[N-:62]

Participants

4

Reactant 2

HCID 89668704HCID 89668704, compoundHCID 117735960((2R,3S,5R)-5-(4-Amino-2-oxopyrimidin-1(2H)-yl)-3-(((((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(hydroxy)phosphoryl)oxy)tetrahydrofuran-2-yl)methyl dihydrogenphosphate tetrabutylammonium salt2×

Product 1

HCID 117735646HCID 117735646, compoundYield 5.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent3×

Procedure

A solution of ((2R,3S,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-3-(((((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methoxy) (hydroxy)phosphoryl)oxy)tetrahydrofuran-2-yl)methyl dihydrogenphosphate (Compound 1h) (30.3 mg, 0.048 mmol) and (2S,5S)-cyanomethyl 6-((((2-azidobenzyl)oxy)carbonyl)amino)-2-((tert-butoxycarbonyl)amino)-5-(methyldisulfanyl)hexanoate (Compound tk16) (77 mg, 0.143 mmol) in acetonitrile (0.7 mL) was added to buffer A (8 mL), and the mixture was stirred at room temperature for 40 minutes. Acetonitrile (3 mL) was added, followed by stirring for 55 minutes. Acetonitrile (2 mL) was further added, followed by stirring for 5 hours. Following lyophilization, 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,5S)-(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-((((2-azidobenzyl)oxy)carbonyl)amino)-2-((tert-butoxycarbonyl)amino)-5-(methyldisulfanyl)hexanoate (Compound tk17) (2.8 mg, 5%).

Workup

  1. stirringby stirring for 55 minutes
  2. stirringby stirring for 5 hours
  3. 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-643db69f0d464146b824fd5864de31f9
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

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