Chlorotrimethylsilane → N2-Isobutyryl-2'-O-Methyl-guanosine

HRID 2212483Notes

Reaction equation

HRID 2212483 reaction equation
[CH3:1][O:2][C@@H:3]1[C@H:7]([OH:8])[C@@H:6]([CH2:9][OH:10])[O:5][C@H:4]1[N:11]1[C:21]2[N:20]=[C:18]([NH2:19])[NH:17][C:15](=[O:16])[C:14]=2[N:13]=[CH:12]1.C[Si](Cl)(C)C.[C:27](Cl)(=[O:31])[CH:28]([CH3:30])[CH3:29].[NH4+].[OH-]>N1C=CC=CC=1.O>[C:27]([NH:19][C:18]1[NH:17][C:15](=[O:16])[C:14]2[N:13]=[CH:12][N:11]([C:21]=2[N:20]=1)[C@@H:4]1[O:5][C@H:6]([CH2:9][OH:10])[C@@H:7]([OH:8])[C@H:3]1[O:2][CH3:1])(=[O:31])[CH:28]([CH3:30])[CH3:29]

Participants

7

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 14923Ammonium HydroxideHCID 62325Isobutyryl chlorideHCID 1354069502'-O-Methylguanosine

Product 1

HCID 135536008N2-Isobutyryl-2'-O-Methyl-guanosine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1049PyridineSolvent

Procedure

2′-O-methylguanosine (3.5 g) in pyridine (100 ml) was treated with trimethylsilyl chloride (9 ml, 6 eq) and isobutyryl chloride (6.2 ml) at RT for 4 hr. The reaction mixture was cooled in an ice bath, H2O (20) was added and stirring continued for an additional 20 min. NH4OH (20 ml) was added and after stirring for 30 min the reaction mixture was evaporated. The residue was triturated with H2O, filtered and the filtrate evaporated and purified by silica gel chromatography as per the procedure of Example 4 to yield the product as an off white solid (1.5 g). 1H NMR (DMSO-d6) δ 1.1 [d, 6, CH(CH3)2], 2.77 [m, 1, CH(CH3)2], 3.33-3.6 (m, 5, OCH3, H-5′), 3.93 (m, 1, H-4′), 4.22 (m, 1), 4.3 (m, 1), 5.1 (t, 1, 5′-OH), 5.28 (d, 1, 3′-OH), 5.9 (d, 1, H-1′), 8.28 (s, 1, H-8) and 11.9 (br s, 1, NH).

Workup

  1. temperatureThe reaction mixture was cooled in an ice bath
  2. stirringafter stirring for 30 min the reaction mixture
  3. customwas evaporated
  4. customThe residue was triturated with H2O
  5. filtrationfiltered
  6. customthe filtrate evaporated
  7. custompurified by silica gel chromatography as per the procedure of Example 4

Sources & evidence

ORD record
ord-978964c25f9349c5bd7b0fb232f03b45
Source dataset
uspto-grants-2006_09
Patent number
US07101993B1

Reaction notes

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