Hydrazine → 9-(2-Aminoethoxymethyl)guanine acetate monohydrate

HRID 2285573Notes

Reaction equation

HRID 2285573 reaction equation
[OH2:1].C1(=O)[N:6]([CH2:7][CH2:8][O:9][CH2:10][N:11]2[CH:19]=[N:18][C:17]3[C:16](=[O:20])[NH:15][C:14]([NH2:21])=[N:13][C:12]2=3)C(=O)C2=CC=CC=C12.NN>C(O)C>[OH2:9].[C:16]([OH:20])(=[O:1])[CH3:17].[NH2:6][CH2:7][CH2:8][O:9][CH2:10][N:11]1[CH:19]=[N:18][C:17]2[C:16](=[O:20])[NH:15][C:14]([NH2:21])=[N:13][C:12]1=2

Participants

4

Reactant 2

HCID 9321HydrazineHCID 1363987959-(2-Phthalimidoethoxymethyl)guanine hydrate

Product 1

HCID 1363987969-(2-Aminoethoxymethyl)guanine acetate monohydrateYield 112.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A dispersion of N-(2-hydroxyethyl)phthalimide (19.1 g) and paraformaldehyde (3.0 g) in 1,2-dichloroethane (250 ml) was cooled in an ice-salt-acetone bath and saturated with dry hydrochloric acid with stirring. After 4 hours the mixture was dried over calcium chloride, filtered and evaporated under reduced pressure to give N-(2-chloromethoxyethyl)phthalimide (21.9 g), m.p. 69°-72° C. To a stirred solution of tris trimethylsilylguanine (16.5 g) in toluene (50 ml) was added N-(2-chloromethoxyethyl)phthalimide (17.0 g) and triethylamine (23 ml). The reaction mixture was heated at reflux under nitrogen for 29 hours, cooled and evaporated under reduced pressure giving a dark brown oil. The oil was digested in ethanol (400 ml) on a steam bath for 40 minutes, giving a solid which was collected and washed with ethanol and ether. It was recrystallized from 2-methoxyethanol to give 9-(2-phthalimidoethoxymethyl)guanine hydrate (14.4 g), m.p.>240° C. (dec.). A mixture of 9-(2-phthalimidoethoxymethyl)guanine hydrate (0.94 g), hydrazine (2 ml) and ethanol (100 ml) was heated at reflux with stirring for one hour. The reaction mixture was filtered hot, and the filtrate was cooled and evaporated under reduced pressure. Ethanol was added and the mixture re-evaporated. This was repeated three times. The residual solid was stirred with 3% aqueous acetic acid (50 ml) for 30 minutes and filtered. The solids were washed with water (15 ml), and the wash and filtrate combined. The combined wash and filtrate was evaporated under reduced pressure at<35° C. to a small volume, diluted with ethanol and evaporated to dryness. The pasty, white solid was dispersed in a small amount of ethanol and diluted with a few ml ether to give a granular solid which was collected, washed with ethanol and dried. Recrystallization from ethanol-water gave 9-(2-aminoethoxymethyl)guanine acetate monohydrate (0.43 g), m.p. (~135° C. melts and resolidifies) 174°-176° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux
  3. filtrationThe reaction mixture was filtered hot
  4. temperaturethe filtrate was cooled
  5. customevaporated under reduced pressure
  6. additionEthanol was added
  7. customthe mixture re-evaporated
  8. stirringThe residual solid was stirred with 3% aqueous acetic acid (50 ml) for 30 minutes
  9. filtrationfiltered
  10. washThe solids were washed with water (15 ml)
  11. washthe wash
  12. washThe combined wash
  13. customfiltrate was evaporated under reduced pressure at<35° C. to a small volume
  14. additiondiluted with ethanol
  15. customevaporated to dryness
  16. additionThe pasty, white solid was dispersed in a small amount of ethanol
  17. additiondiluted with a few ml ether
  18. customto give a granular solid which
  19. customwas collected
  20. washwashed with ethanol
  21. customdried
  22. customRecrystallization from ethanol-water

Sources & evidence

ORD record
ord-0764d26e24994d65a8c328c281a238d9
Source dataset
uspto-grants-1982_04
Patent number
US04323573

Reaction notes

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