Phenyl isocyanate → 5'-O-[bis(4-methoxyphenyl)phenylmethyl]-N2-phenoxyacetyl-3'-O-phenylcarbamoylguanosine

HRID 889778

Reaction equation

HRID 889778 reaction equation
C([C@H]1COC(C2C=CC=C(C3OC[C@H](C(C)C)N=3)N=2)=N1)(C)C.[CH3:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]([C:68]2[CH:73]=[CH:72][C:71]([O:74][CH3:75])=[CH:70][CH:69]=2)([C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)[O:32][CH2:33][C@H:34]2[O:38][C@@H:37]([N:39]3[C:59]4[N:58]=[C:46]([NH:47][C:48](=[O:57])[CH2:49][O:50][C:51]5[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=5)[NH:45][C:43](=[O:44])[C:42]=4[N:41]=[CH:40]3)[C@H:36]([OH:60])[C@@H:35]2[OH:61])=[CH:27][CH:26]=1.[C:76]1([N:82]=[C:83]=[O:84])[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=1.C([O-])([O-])=O.[K+].[K+].COC1C=CC(C(C2C=CC(OC)=CC=2)(C2C=CC=CC=2)OC[C@H]2O[C@@H](N3C4N=C(NC(=O)COC5C=CC=CC=5)NC(=O)C=4N=C3)[C@H](OC(=O)NC3C=CC=CC=3)[C@@H]2O)=CC=1>C(S([O-])(=O)=O)(F)(F)F.C(S([O-])(=O)=O)(F)(F)F.[Cu+2].C1COCC1>[CH3:75][O:74][C:71]1[CH:70]=[CH:69][C:68]([C:31]([C:28]2[CH:27]=[CH:26][C:25]([O:24][CH3:23])=[CH:30][CH:29]=2)([C:62]2[CH:63]=[CH:64][CH:65]=[CH:66][CH:67]=2)[O:32][CH2:33][C@H:34]2[O:38][C@@H:37]([N:39]3[C:59]4[N:58]=[C:46]([NH:47][C:48](=[O:57])[CH2:49][O:50][C:51]5[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=5)[NH:45][C:43](=[O:44])[C:42]=4[N:41]=[CH:40]3)[C@H:36]([OH:60])[C@@H:35]2[O:61][C:83](=[O:84])[NH:82][C:76]2[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=2)=[CH:73][CH:72]=1

Participants

8

Reactant 5

HCID 7672Phenyl isocyanate2×HCID 11430Potassium CarbonateHCID 688211(S,S)-2,6-Bis(4-isopropyl-2-oxazolin-2-yl)pyridineHCID 136368406N2-Phenoxyacetyl-5'-O-(4,4'-dimethoxytrityl)guanosineHCID 1363978965'-O-[bis(4-methoxyphenyl)phenylmethyl]-N2-phenoxyacetyl-2'-O-phenylcarbamoylguanosine

Product 1

HCID 1363978905'-O-[bis(4-methoxyphenyl)phenylmethyl]-N2-phenoxyacetyl-3'-O-phenylcarbamoylguanosine

Reagents, catalysts & solvents 2

HCID 2734996copper(II) trifluoromethanesulfonateCatalystHCID 8028TetrahydrofuranSolvent4×

Procedure

The THF solution (33 ml) containing 2,6-bis[(4S)-isopropyl-2-oxazoline-2-yl]pyridine (0.06 mmol, 18.1 mg) and copper chloride (II) (0.06 mmol, 10.2 mg) was stirred for a day at room temperature. After the reaction mixture was cooled to −20° C., the THF solution (32 ml) of 5′-O-[bis(4-methoxyphenyl)phenylmethyl]-N2-phenoxyacetyl-guanosine (0.60 mmol, 431.8 mg) and the THF solution (1.6 ml) of phenyl isocyanate (0.60 mmol, 71.5 mg) and K2CO3 (0.60 mmol, 82.9 mg) were sequentially added thereto. After the mixture was stirred for 24.5 hours at −20° C., the THF solution (1.6 ml) of phenyl isocyanate (0.60 mmol, 71.5 mg) was added thereto. After the mixture was further stirred for 23.5 hours, the mixture was analyzed with high-performance liquid chromatography. As a result, it was found that 5′-O-[bis(4-methoxyphenyl)phenylmethyl]-N2-phenoxyacetyl-2′-O-phenylcarbamoylguanosine and 5′-O-[bis(4-methoxyphenyl)phenylmethyl]-N2-phenoxyacetyl-3′-O-phenylcarbamoylguanosine were produced at the ratio of 99:1, and the transformation ratio of the reaction was not less than 99%.

Workup

  1. temperatureAfter the reaction mixture was cooled to −20° C.
  2. stirringAfter the mixture was stirred for 24.5 hours at −20° C.
  3. stirringAfter the mixture was further stirred for 23.5 hours

Sources & evidence

ORD record
ord-cf14502cf9a843679917458ba481868b
Source dataset
uspto-grants-2012_08
Patent number
US08252919B2

Linked notes

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