Triethylamine → 9-(2-Phthalimidoethoxymethyl)guanine hydrate

HRID 2198930Notes

Reaction equation

HRID 2198930 reaction equation
C[Si]([C:5]1[NH:13][C:12]2[C:11](=[O:14])[NH:10][C:9]([N:15]([Si](C)(C)C)[Si](C)(C)C)=[N:8][C:7]=2[N:6]=1)(C)C.Cl[CH2:25][O:26][CH2:27][CH2:28][N:29]1[C:33](=[O:34])[C:32]2=[CH:35][CH:36]=[CH:37][CH:38]=[C:31]2[C:30]1=[O:39].C(N(CC)CC)C>C1(C)C=CC=CC=1.C(O)C>[OH2:14].[C:30]1(=[O:39])[N:29]([CH2:28][CH2:27][O:26][CH2:25][N:6]2[CH:5]=[N:13][C:12]3[C:11](=[O:14])[NH:10][C:9]([NH2:15])=[N:8][C:7]2=3)[C:33](=[O:34])[C:32]2=[CH:35][CH:36]=[CH:37][CH:38]=[C:31]12

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 12926790N-(2-chloromethoxyethyl)phthalimideHCID 136139236Tris-(trimethylsilyl)guanine

Product 1

HCID 1363987959-(2-Phthalimidoethoxymethyl)guanine hydrateYield 172.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

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. temperatureThe reaction mixture was heated
  2. temperatureat reflux under nitrogen for 29 hours
  3. temperaturecooled
  4. customevaporated under reduced pressure
  5. customgiving a dark brown oil
  6. customgiving a solid which
  7. customwas collected
  8. washwashed with ethanol and ether
  9. customIt was recrystallized from 2-methoxyethanol

Sources & evidence

ORD record
ord-06f1e04f8b1b4eec9695b3ca0b8d89bc
Source dataset
uspto-grants-1982_11
Patent number
US04360522

Reaction notes

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