Potassium Hydroxide → Diazoethane

HRID 879954Notes

Reaction equation

HRID 879954 reaction equation
[CH2:1]([N:3]([N:10]=O)C(N[N+]([O-])=O)=N)[CH3:2].[OH-].[K+].[NH2:14][C:15]1[N:19]([C@@H:20]2[O:26][C@H:25]([CH2:27][OH:28])[C@@H:23]([OH:24])[C@H:21]2[OH:22])[CH:18]=[N:17][C:16]=1[C:29]([NH2:31])=[O:30].O.O.[Sn](Cl)Cl>CCOCC.CN(C)C=O.CO.O>[N+:3](=[CH:1][CH3:2])=[N-:10].[NH2:14][C:15]1[N:19]([C@@H:20]2[O:26][C@H:25]([CH2:27][OH:28])[C@@H:23]([OH:24])[C@H:21]2[O:22][CH2:1][CH3:2])[CH:18]=[N:17][C:16]=1[C:29]([NH2:31])=[O:30]

Participants

10

Reactant 4

HCID 14797Potassium HydroxideHCID 17513AcadesineHCID 61436Stannous chloride dihydrateHCID 135510215N-Ethyl-N'-nitro-N-nitrosoguanidine

Product 2

HCID 70695DiazoethaneHCID 186627915-amino-1-(2-O-ethyl-beta-D-ribofuranosyl) imidazole-4-carboxamide

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
4 °C

Procedure

A solution of approximately 30 mmol diazoethane in 40 ml of ether was prepared by slow addition of 7 g (44 mmol) of 1-ethyl-3-nitro-1-nitrosoguanidine to a mixture of 8 g of potassium hydroxide, 9 ml water and 60 ml of ether followed by distillation. This was slowly added to a solution of 3.2 g (12 mmol) of 5-amino-1-β-D-ribofuranosylimidazole-4-carboxamide (AICA riboside) in 35 ml dimethylformamide containing 50 mg of tin(II) chloride dihydrate. During the addition approximately 20 ml of methanol was added to maintain solubility. The reaction was filtered to remove a trace precipitate and evaporated to a yellow syrup. Thin layer chromatography on silica gel using methylene chloride/methanol (3:1) showed a major product spot moving faster than AICA riboside. The syrup was chromatographed on silica gel using methylene chloride/methanol (8:1) collecting the major product as determined by TLC. The appropriate fractions were evaporated to a white foam. This was dissolved in 7 ml of methanol. Upon cooling to 4° C. the mixture crystallized to yield 160 mg of 5-amino-1-(2-O-ethyl-β-D-ribofuranosyl) imidazole-4-carboxamide (Compound No. 34 (1-250)) confirmed by NMR decoupling and exchange experiments.

Workup

  1. distillationfollowed by distillation
  2. additionwas added
  3. temperatureto maintain solubility
  4. filtrationThe reaction was filtered
  5. customto remove a trace precipitate
  6. customevaporated to a yellow syrup
  7. customThe syrup was chromatographed on silica gel
  8. customcollecting the major product
  9. customThe appropriate fractions were evaporated to a white foam
  10. dissolutionThis was dissolved in 7 ml of methanol
  11. customcrystallized

Sources & evidence

ORD record
ord-0226f4bfefff4fe9aaf372d4182a9b8e
Source dataset
uspto-grants-2015_03
Patent number
US08993527B2

Reaction notes

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