Cyanoacetic acid → 6-Amino-1,3-bis(cyclohexylmethyl)uracil

HRID 396262Notes

Reaction equation

HRID 396262 reaction equation
[C:1]([CH2:3][C:4](O)=[O:5])#[N:2].[CH:7]1([CH2:13][NH:14][C:15]([NH:17][CH2:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)=[O:16])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1>C(OC(=O)C)(=O)C>[NH2:2][C:1]1[N:14]([CH2:13][CH:7]2[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]2)[C:15](=[O:16])[N:17]([CH2:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[C:4](=[O:5])[CH:3]=1

Participants

4

Reactant 2

HCID 9740Cyanoacetic acidHCID 2315151,3-Bis(cyclohexylmethyl)urea

Product 1

HCID 222449716-Amino-1,3-bis(cyclohexylmethyl)uracilYield 94.2%

Reagents, catalysts & solvents 1

HCID 7918Acetic AnhydrideSolvent

Conditions

Temperature
80 °C

Procedure

Cyanoacetic acid (Aldrich, 21.0 g) was dissolved in acetic anhydride (260 ml). This solution was added to 1,3-bis(cyclohexylmethyl)urea (from step (a), 54.5 g) and the solution maintained at 80° C. for 2 h under nitrogen. Volatiles were removed in vacuo and the residual oil dried by evaporation of portions of 10% water-ethanol (3×400 ml). The residual solids were dissolved in ethanol (600 ml)water(300 ml) at 80° C. with adjustment of the pH to 10 by addition of 10% aqueous sodium carbonate. The hot solution was diluted with water (75 ml) and cooled to ambient temperature. The colorless crystals which formed were filtered off, washed with water and dried at 0.5 Torr to give 6-amino-1,3-bis(cyclohexylmethyl)uracil (64.98 g, 94%), m.p. 138-141° C.; 1H-NMR (DMSO-d6) δ: 6.73 (br s, 2, NH2), 4.63 (s, 1, H-5), 3.67 (d, J=7.3 Hz, 2, NCH2), 3.57 (d, J=7.3 Hz, 2, NCH2), 1.55 and 1.09 (both m, 22, 2 cyclohexyl).

Workup

  1. customVolatiles were removed in vacuo
  2. dry with materialthe residual oil dried by evaporation of portions of 10% water-ethanol (3×400 ml)
  3. dissolutionThe residual solids were dissolved in ethanol (600 ml)water(300 ml) at 80° C. with adjustment of the pH to 10 by addition of 10% aqueous sodium carbonate
  4. additionThe hot solution was diluted with water (75 ml)
  5. temperaturecooled to ambient temperature
  6. customThe colorless crystals which formed
  7. filtrationwere filtered off
  8. washwashed with water
  9. customdried at 0.5 Torr

Sources & evidence

ORD record
ord-fce726559883443192e590b2e12764cd
Source dataset
uspto-grants-2003_08
Patent number
US06608069B1

Reaction notes

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