Hydrochloric Acid → HCID 10905167, compound

HRID 488533Notes

Reaction equation

HRID 488533 reaction equation
[CH2:1]([N:8]1[C:25]([NH2:26])=[N:24][C:23]2[N:13]([C@@H:14]3[O:22][C@H:19]([CH2:20][OH:21])[C@@H:17]([OH:18])[C@H:15]3[OH:16])[CH:12]=[N:11][C:10]=2[C:9]1=[O:27])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[SiH](C)(C)[CH3:29].Cl>C/C(/O)=C/C(C)=O.[Ag].CN(C)C=O>[CH2:1]([N:8]1[C:25]([NH2:26])=[N:24][C:23]2[N:13]([C@@H:14]3[O:22][C@H:19]([CH2:20][OH:21])[C@@H:17]([OH:18])[C@H:15]3[O:16][CH3:29])[CH:12]=[N:11][C:10]=2[C:9]1=[O:27])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 70435TrimethylsilaneHCID 11143242HCID 11143242, compound

Product 1

HCID 10905167HCID 10905167, compound

Reagents, catalysts & solvents 2

HCID 11074572HCID 11074572, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A 1 L pear shaped recovery flask with stir bar was charged with a mixture of 16 (50 g, 134 mmol), silver acetylacetonate (41 g 200 mmol), TMSH (200 ml of 1N solution in methanol) and dimethylformamide (400 ml). The flask was heated to 70° C. for two hours. The solution was cooled to ambient temperature, neutralized to pH 7 with 1M HCl, and dried to a solid tar. The tar was dissolved in water (500 ml) and filtered through a sintered glass funnel to remove silver salts. The product was evaporated to dryness to remove water and residual solvents and 10 grams (26 mmols) was redissolved in 50 ml of water prior to purification on a Waters Delta-Pak ODS 50 mm×300 mm HPLC column. The N1-Bz-2′-OMe guanosine isomer eluted first and was recovered using a rotary evaporator. The product (7 g, 18 mm, 70%) was identical to an authentic sample by HPLC, UV-, 1H-NMR-spectroscopy. 1H NMR (dmso-d6): 8.02 (s, 1H, H8), 7.26 (m, 5H, ph), 7.02 (bs, 2H, 2NH2), 5.82 (d, J1′,2′=6.4, 1H, H1′), 5.23 (s, 2H, CH2-Bz), 5.18 (d, JOH,3′=4.8, 1H, 3′-OH), 5.04 (t, JOH,5′=5.2, JOH,5″=5.6, 1H, 5′-OH), 4.28 (m, J3′,2′=4.8, J3′,4′=3.2, 1H, H3′), 4.20 (t, J2′,1′=6.4, J2′,3′=4.8, 1H, H2′), 3.90 (m, J4′,3′=3.6, J4′,5′=4.0, 1H, H4′), 3.65-3.53 (m, 2H, H5′, H5″ JOH,5′=5.2, J5′,5″=11.6), 3.33 (s, 3H, OCH3).

Workup

  1. temperatureThe solution was cooled to ambient temperature
  2. customdried to a solid tar
  3. dissolutionThe tar was dissolved in water (500 ml)
  4. filtrationfiltered through a sintered glass funnel
  5. customto remove silver salts
  6. customThe product was evaporated to dryness
  7. customto remove water and residual solvents and 10 grams (26 mmols)
  8. dissolutionwas redissolved in 50 ml of water
  9. customto purification on a Waters Delta-Pak ODS 50 mm×300 mm HPLC column
  10. washThe N1-Bz-2′-OMe guanosine isomer eluted first
  11. customwas recovered
  12. customa rotary evaporator

Sources & evidence

ORD record
ord-266f9f20cbb545769e6a4ad6cafe94bb
Source dataset
uspto-grants-2005_12
Patent number
US06972330B2

Reaction notes

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