Acetic Acid → Ethyl 4-[[3-(2,4-diamino-1,6-dihydro-6-oxo-5-pyrimidinyl)propyl]thio]benzoate

HRID 1649772Notes

Reaction equation

HRID 1649772 reaction equation
Cl.[NH2:2][C:3]([NH2:5])=[NH:4].[O-]CC.[Na+].[C:10]([CH:12]([C:28](OCC)=[O:29])[CH2:13][CH2:14][CH2:15][S:16][C:17]1[CH:27]=[CH:26][C:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:19][CH:18]=1)#[N:11].C(O)(=O)C>C(O)C>[NH2:4][C:3]1[NH:5][C:28](=[O:29])[C:12]([CH2:13][CH2:14][CH2:15][S:16][C:17]2[CH:18]=[CH:19][C:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:26][CH:27]=2)=[C:10]([NH2:11])[N:2]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5742Guanidine HydrochlorideHCID 2723922Sodium ethoxideHCID 14751115HCID 14751115, compound

Product 1

HCID 135976864Ethyl 4-[[3-(2,4-diamino-1,6-dihydro-6-oxo-5-pyrimidinyl)propyl]thio]benzoateYield 95.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

Dry guanidine hydrochloride (3.43 g, 35.9 mmoles) was added to a solution of sodium ethoxide 53.5 mmoles) in ethanol (25 mL), and the mixture was treated with 1B (6.00 g, 17.9 mmoles) as a solution in ethanol (25 mL) and refluxed for 5 hours. After cooling, the pH was adjusted to 7.0 with acetic acid, and the mixture was evaporated to a viscous residue in vacuo. The residue was treated with water (70 mL) and was filtered to give an off white solid, which was washed with 3 volumes (30 mL) of water and 3 volumes (30 mL) of ether and was dried in vacuo to give crude product title compound, 1C, (5.96 g, 95%) as a white solid. NMR (DMSO-d6) δ1.3 (t, 3H, CH3 of ester), 1.65 (m, 2H, CH2 --CH2 --CH2), 2.3 (t, 2H, CH2 --CH2 --CH2 --S), 2.95 (m, 2H, CH2 --S), 4.3 (q, 2H, CH2 of ester), 5.7 (br s, 2H, NH2), 5.95 (br s, 2H, NH2), 7.3 (d, 2H) (benzoate H's ortho to sulfur), 7.85 (d, 1H, 7.95 (d, 1H), 9.8 (br s, 1H, ring NH). The aromatic region of the NMR spectrum indicated slight impurities; compound 1C was used in the next reaction without further purification.

Workup

  1. temperaturerefluxed for 5 hours
  2. temperatureAfter cooling
  3. customthe mixture was evaporated to a viscous residue in vacuo
  4. additionThe residue was treated with water (70 mL)
  5. filtrationwas filtered
  6. customto give an off white solid, which
  7. washwas washed with 3 volumes (30 mL) of water and 3 volumes (30 mL) of ether
  8. customwas dried in vacuo

Sources & evidence

ORD record
ord-3e92daf6d2e54f75b6fee81f38e718f1
Source dataset
uspto-grants-1990_05
Patent number
US04921836

Reaction notes

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