Barbituric Acid → (4'R,6'S,7'S)-17'-fluoro-4',6'-dimethyl-13'-(1,2,4-triazol-1-yl)spiro[1,3-diazinane-5,8'-5,15-dioxa-2,14-diazatetracyclo[8.7.0.02,7.012,16]heptadeca-1(17),10,12(16),13-tetraene]-2,4,6-trione

HRID 578013Notes

Reaction equation

[CH3:1][C@@H:2]1[CH2:7][N:6]([C:8]2[C:21]([CH:22]=O)=[CH:20][C:11]3[C:12]([N:15]4[CH:19]=[N:18][CH:17]=[N:16]4)=[N:13][O:14][C:10]=3[C:9]=2[F:24])[CH2:5][C@@H:4]([CH3:25])[O:3]1.[NH:26]1[C:31](=[O:32])[CH2:30][C:29](=[O:33])[NH:28][C:27]1=[O:34]>CS(C)=O>[F:24][C:9]1[C:10]2[O:14][N:13]=[C:12]([N:15]3[CH:19]=[N:18][CH:17]=[N:16]3)[C:11]=2[CH:20]=[C:21]2[C:8]=1[N:6]1[CH2:5][C@@H:4]([CH3:25])[O:3][C@@H:2]([CH3:1])[C@@H:7]1[C:30]1([C:29](=[O:33])[NH:28][C:27](=[O:34])[NH:26][C:31]1=[O:32])[CH2:22]2

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of 6-((2R,6R)-2,6-dimethylmorpholino)-7-fluoro-3-(1H-1,2,4-triazol-1-yl)benzo[d]isoxazole-5-carbaldehyde (Intermediate 574, 500 mg, 1.45 mmol) and pyrimidine-2,4,6(1H,3H,5H)-trione (185 mg, 1.45 mmol) in DMSO (6 ml) was heated at 150° C. for 2 hours in a microwave reactor. The reaction mixture was purified by Super Critical Fluid chromatography on a Chiralpac IC column with a 35% MeOH, 65% CO2 mobile phase to give 290 mg of product as a solid as the first eluting compound.

Workup

customThe reaction mixture was purified by Super Critical Fluid chromatography on a Chiralpac IC column with a 35% MeOH, 65% CO2 mobile phase

Sources & evidence

ORD record: ord-baf62cd73e1e484f88c24fd1d7d053a2
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040528B2

Reaction notes

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