Hydrochloric Acid → 1,3-Dibutylxanthine

HRID 965188Notes

Reaction equation

HRID 965188 reaction equation
[NH2:1][C:2]1[N:7]([CH2:8][CH2:9][CH2:10][CH3:11])[C:6](=[O:12])[N:5]([CH2:13][CH2:14][CH2:15][CH3:16])[C:4](=[O:17])[C:3]=1[N:18]=O.Cl.[CH3:21]N(C)CCCN=C=NCC.[OH-].[Na+].Cl>CN(C=O)C.[Pd].C(O)=O>[CH2:13]([N:5]1[C:4](=[O:17])[C:3]2[NH:18][CH:21]=[N:1][C:2]=2[N:7]([CH2:8][CH2:9][CH2:10][CH3:11])[C:6]1=[O:12])[CH2:14][CH2:15][CH3:16]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 3860046-Amino-1,3-dibutyl-5-nitroso-2,4(1H,3H)-pyrimidinedioneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 1014211,3-DibutylxanthineYield 151.6%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 284Formic AcidSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 6-amino-1,3-di-n-butyl-5-nitroso-uracil (3.1 g, 11.6 mmol) and 5% Pd-C in dry DMF (30 ml) was hydrogenated at 50 psi until it became a colorless solution (about 2 h). The catalyst was filtered off through Celite pad and the filtrate was mixed with 88% formic acid (15 ml) and 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (1.1 g, 5.74 mmol) at 0° C. under nitrogen. The violet solution was stirred at room temperature for 3 h. DMF and formic acid were removed by rotary evaporation and the solid residue was mixed with 2N sodium hydroxide (50 ml, 100 mmol). The reaction mixture was heated at reflux for 1 h. The yellow solution was cooled and neutralized with 6N hydrochloric acid to pH 3. The solid was collected by filtration, washed with water, and dried to yield 1,3-di-n-butyl-xanthine (2.3 g, 75%), m.p. 165.5°-169° C.; 1H NMR (DMSO-d6) δ1.41-1.47 (m, 6H, 2×CH3), 1.61-1.68 (m, 4H, 2×CH2), 1.74-1.79 (m, 2H, CH2), 1.82-1.85 (m, 2H, CH2), 3.84 (t, 2H, N--CH2), 3.98 (t, 2H, N--CH2), 8.10 (s, 1H, H-8), 13.7 (br s, 1H, NH).

Workup

  1. customa colorless solution (about 2 h)
  2. filtrationThe catalyst was filtered off through Celite pad
  3. customDMF and formic acid were removed by rotary evaporation
  4. temperatureThe reaction mixture was heated
  5. temperatureat reflux for 1 h
  6. temperatureThe yellow solution was cooled
  7. filtrationThe solid was collected by filtration
  8. washwashed with water
  9. customdried

Sources & evidence

ORD record
ord-c2936e1c3c6245d7ad65b715a01571e5
Source dataset
uspto-grants-1998_06
Patent number
US05773423

Reaction notes

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