Hydrochloric Acid → 5-Methylisocytosine

HRID 1524838Notes

Reaction equation

HRID 1524838 reaction equation
[CH3:1][O-].[Na+].[C:4]([O:8]CC)(=O)[CH2:5][CH3:6].C(OC)=O.Cl.[NH2:16][C:17]([NH2:19])=[NH:18].Cl>CN(C=O)C.CO>[CH3:1][C:5]1[C:4](=[O:8])[NH:16][C:17]([NH2:19])=[N:18][CH:6]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 5742Guanidine HydrochlorideHCID 7749Ethyl PropionateHCID 7865Methyl formateHCID 10942334Sodium Methoxide

Product 1

HCID 852215-MethylisocytosineYield 58.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
30 °C

Procedure

Freshly prepared sodium methoxide (10.8 g, 200 mmol) was suspended in a solution of ethyl propionate (15.3 g, 150 mmol) in DMF (20 mL) at room temperature. Methyl formate (6.0 g, 100 mmol) was added over a period of 1 hour. After stirring for 30 minutes, a solution of guanidine hydrochloride (9.6 g, 100 mmol) in MeOH (35 mL) was added rapidly and the reaction mixture was refluxed for 12 hours. After cooling to 30° C. and adjusting the pH to 6.0 with concentrated hydrochloric acid, the slurry was kept at 5° C. for 30 minutes. The solid was collected, washed with methanol, crystallized from water and dried in vacuo to give 5-methylisocytosine (7.3 g, 58.4% yield). 1H NMR (300 MHz, DMSO): 610.83 (br s, 2 H), 7.38 (s, 1 H), 6.26 (br s, 2 H), 1.72 (s, 3 H).

Workup

  1. temperaturethe reaction mixture was refluxed for 12 hours
  2. waitthe slurry was kept at 5° C. for 30 minutes
  3. customThe solid was collected
  4. washwashed with methanol
  5. customcrystallized from water
  6. customdried in vacuo

Sources & evidence

ORD record
ord-11ca0860a1234c199011d37acd7986b7
Source dataset
uspto-grants-2015_07
Patent number
US09079916B2

Reaction notes

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