Barbituric Acid → (2r,4s,4As)-8-acetyl-9,10-difluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2'h,6h-spiro[1,4-oxazino[4,3-a]quinoline-5,5'-pyrimidine]-2',4',6'(1'h,3'h)-trione

HRID 245359

Reaction equation

HRID 245359 reaction equation
[C:1]([C:4]1[C:5]([F:21])=[C:6]([F:20])[C:7]([N:12]2[CH2:17][C@H:16]([CH3:18])[O:15][C@H:14]([CH3:19])[CH2:13]2)=[C:8]([CH:11]=1)[CH:9]=O)(=[O:3])[CH3:2].[NH:22]1[C:29](=[O:30])[CH2:28][C:26](=[O:27])[NH:25][C:23]1=[O:24]>CC(O)C>[C:1]([C:4]1[CH:11]=[C:8]2[C:7](=[C:6]([F:20])[C:5]=1[F:21])[N:12]1[CH2:17][C@@H:16]([CH3:18])[O:15][C@@H:14]([CH3:19])[C@@H:13]1[C:28]1([C:26](=[O:27])[NH:25][C:23](=[O:24])[NH:22][C:29]1=[O:30])[CH2:9]2)(=[O:3])[CH3:2]

Participants

4

Reactant 2

HCID 6211Barbituric AcidHCID 588470585-acetyl-2-((2R,6S)-2,6-dimethyl-morpholin-4-yl)-3,4-difluoro-benzaldehyde2×

Product 1

HCID 58847042(2r,4s,4As)-8-acetyl-9,10-difluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2'h,6h-spiro[1,4-oxazino[4,3-a]quinoline-5,5'-pyrimidine]-2',4',6'(1'h,3'h)-trione

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of 5-acetyl-2-((2R,6S)-2,6-dimethyl-morpholin-4-yl)-3,4-difluoro-benzaldehyde (Intermediate 11, 3.0 g, 9.17 mmol) in IPA was added barbituric acid (1.4 g, 11.00 mmol), and the mixture was heated at 85° C. for 12 hours. Solvents were evaporated and the residue was purified over neutral alumina using a gradient of methanol in CH2Cl2 to give the title compound as a racemic mixture in the form of an off-white solid. Yield: 3.0 g (75%).

Workup

  1. customSolvents were evaporated
  2. customthe residue was purified over neutral alumina using a gradient of methanol in CH2Cl2

Sources & evidence

ORD record
ord-3a2ef7a8c82541e096659b691eb6fea3
Source dataset
uspto-grants-2014_02
Patent number
US08658641B2

Linked notes

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