Barbituric Acid → (2R,4S,4aS)-8-chloro-11-fluoro-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1'H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5'-pyrimidine]-2',4',6'(3'H)-trione

HRID 245575Notes

Reaction equation

HRID 245575 reaction equation
[Cl:1][C:2]1[C:6]2[CH:7]=[C:8]([CH:20]=O)[C:9]([N:12]3[CH2:17][C@@H:16]([CH3:18])[O:15][C@H:14]([CH3:19])[CH2:13]3)=[C:10]([F:11])[C:5]=2[O:4][N:3]=1.[NH:22]1[C:27](=[O:28])[CH2:26][C:25](=[O:29])[NH:24][C:23]1=[O:30]>CC(O)C>[Cl:1][C:2]1[C:6]2[CH:7]=[C:8]3[C:9](=[C:10]([F:11])[C:5]=2[O:4][N:3]=1)[N:12]1[CH2:17][C@@H:16]([CH3:18])[O:15][C@@H:14]([CH3:19])[C@@H:13]1[C:26]1([C:25](=[O:29])[NH:24][C:23](=[O:30])[NH:22][C:27]1=[O:28])[CH2:20]3

Participants

4

Reactant 2

HCID 6211Barbituric AcidHCID 866581223-chloro-6-((2R,6R)-2,6-dimethylmorpholino)-7-fluorobenzo[d]isoxazole-5-carbaldehyde2×

Product 1

HCID 67432893(2R,4S,4aS)-8-chloro-11-fluoro-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1'H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5'-pyrimidine]-2',4',6'(3'H)-trioneYield 26.5%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of 3-chloro-6-((2R,6R)-2,6-dimethylmorpholino)-7-fluorobenzo[d]isoxazole-5-carbaldehyde (Intermediate 535, 764 mg, 2.44 mmol) and pyrimidine-2,4,6(1H,3H,5H)-trione (313 mg, 2.44 mmol) in iPrOH (3 ml) was heated at reflux for 3 days. Solvent was removed and the residue was recrystallized from methanol. The solids obtained were recrystallized from 1:1 EtOH-Water to afford 273 mg of product consistent with desired product.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 3 days
  3. customSolvent was removed
  4. customthe residue was recrystallized from methanol
  5. customThe solids obtained
  6. customwere recrystallized from 1:1 EtOH-Water

Sources & evidence

ORD record
ord-69431771947a42c1834895cc325b229a
Source dataset
uspto-grants-2014_02
Patent number
US08658641B2

Reaction notes

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