5'-Phospho-2'-deoxyribocytidylylriboadenosine → (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-(N-methylpent-4-enamido)acetate

HRID 1482382Notes

Reaction equation

HRID 1482382 reaction equation
[P:1]([O:5][CH2:6][C@@H:7]1[C@@H:11]([O:12][P:13]([O:16][CH2:17][C@@H:18]2[C@@H:22]([OH:23])[C@@H:21]([OH:24])[C@H:20]([N:25]3[CH:33]=[N:32][C:31]4[C:26]3=[N:27][CH:28]=[N:29][C:30]=4[NH2:34])[O:19]2)([OH:15])=[O:14])[CH2:10][C@H:9]([N:35]2[CH:40]=[CH:39][C:38]([NH2:41])=[N:37][C:36]2=[O:42])[O:8]1)([OH:4])([OH:3])=[O:2].C([N+](CCCC)(CCCC)CCCC)CCC.P(OC[C@@H]1[C@@H](OP(OC[C@@H]2[C@@H](O)[C@@H](O)[C@H](N3C=NC4C3=NC=NC=4N)O2)(O)=O)C[C@H](N2C=CC(N)=NC2=O)O1)(O)(O)=O.[CH3:102][N:103]([CH2:110][C:111](OCC#N)=[O:112])[C:104](=[O:109])[CH2:105][CH2:106][CH:107]=[CH2:108]>O1CCCC1>[CH3:102][N:103]([CH2:110][C:111]([O:23][C@H:22]1[C@@H:21]([OH:24])[C@H:20]([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:19][C@@H:18]1[CH2:17][O:16][P:13]([O:12][C@H:11]1[CH2:10][C@H:9]([N:35]2[CH:40]=[CH:39][C:38]([NH2:41])=[N:37][C:36]2=[O:42])[O:8][C@@H:7]1[CH2:6][O:5][P:1]([OH:4])([OH:3])=[O:2])([OH:15])=[O:14])=[O:112])[C:104](=[O:109])[CH2:105][CH2:106][CH:107]=[CH2:108]

Participants

5

Reactant 3

HCID 1955115'-Phospho-2'-deoxyribocytidylylriboadenosineHCID 89668754cyanomethyl 2-(N-methylpent-4-enamido)acetateHCID 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 89668667(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-(N-methylpent-4-enamido)acetateYield 11.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

((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) (Compound 1h) (1.00 g, 1.57 mmol) was dissolved in buffer A (1 l), a solution of cyanomethyl 2-(N-methylpent-4-enamido)acetate (Compound SP704) (2.00 g, 9.51 mmol) in tetrahydrofuran (5 ml) was added and the mixture was stirred at room temperature for 30 minutes. The reaction solution was lyophilized, and the resulting residue was purified by reverse-phase silica gel column chromatography (0.5% aqueous trifluoroacetic acid solution/acetonitrile) to afford the title compound (Compound SP705) (139 mg, 11%).

Workup

  1. customthe resulting residue was purified by reverse-phase silica gel column chromatography (0.5% aqueous trifluoroacetic acid solution/acetonitrile)

Sources & evidence

ORD record
ord-709edf2996ed47e1b8fcc8991a5ec476
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

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