Acetone → 2-(2,6-Dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxamido)-4-methylpentanoic acid

HRID 883535Notes

Reaction equation

HRID 883535 reaction equation
[C:1](Br)(=[O:10])[C:2]1[NH:9][C:7](=[O:8])[NH:6][C:4](=[O:5])[CH:3]=1.[NH2:12][C@H:13]([C:18]([OH:20])=[O:19])[CH2:14][CH:15]([CH3:17])[CH3:16].C(=O)=O.CC(C)=O>C(Cl)Cl.CN(C1C=CN=CC=1)C>[O:8]=[C:7]1[NH:9][C:2]([C:1]([NH:12][CH:13]([CH2:14][CH:15]([CH3:17])[CH3:16])[C:18]([OH:20])=[O:19])=[O:10])=[CH:3][C:4](=[O:5])[NH:6]1

Participants

7

Reactant 4

HCID 180AcetoneHCID 280Carbon DioxideHCID 6106L-LeucineHCID 461847302,6-Dioxo-1,2,3,6-tetrahydropyrimidine-4-carbonyl bromide4×

Product 1

HCID 247006732-(2,6-Dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxamido)-4-methylpentanoic acid

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

In a dry 3-necked, round bottomed flask, equipped with a magnetic stirrer, a thermometer, a nitrogen inlet tube and the dropping funnel containing the orotoyl bromide solution, 5.90 g (45 mmol) of Leucine is suspended, with stirring, in 50 mL of dry DCM. To this suspension a catalytic amount (˜0.1 mmol) of DMAP is also added. The suspension is stirred in a dry ice and acetone bath to a temperature of about −15° C. When the target temperature is reached the drop wise addition of orotoyl bromide is commenced. Addition of orotoyl bromide continues, with constant cooling and stirring, until all of the orotoyl bromide is added, after which the reaction is allowed to warm to room temperature with constant agitation. The solution is then filtered to remove any remaining Leucine and the volatile DCM is removed from the filtrate under reduced pressure, the remainder is then purified by flash chromatography (ethyl acetate/hexanes; 1/5), yielding 2-(2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxamido)-4-methylpentanoic acid.

Workup

  1. customIn a dry 3-necked, round bottomed flask, equipped with a magnetic stirrer
  2. temperaturewith constant cooling
  3. filtrationThe solution is then filtered
  4. customto remove any remaining Leucine
  5. customthe volatile DCM is removed from the filtrate under reduced pressure
  6. customthe remainder is then purified by flash chromatography (ethyl acetate/hexanes; 1/5)

Sources & evidence

ORD record
ord-48e91d8f3be1400789a11d60fc164d17
Source dataset
uspto-grants-2012_08
Patent number
US08236952B2

Reaction notes

Loading…