Dimethyl Sulfate → 1,3,6-Trimethyl-2,4(1H,3H)-pyrimidinedione

HRID 1912350Notes

Reaction equation

CC1OC(C2NC3C(=CC=CC=3)N3[C:8]2=[C:9]2[N:31]([CH3:32])[C:29](=[O:30])[N:28]([CH3:33])[C:26](=[O:27])[C:10]2=C3C2C=CC=CC=2)=CC=1.CC1NC(=O)NC(=O)C=1.COS(OC)(=O)=O>>[CH3:32][N:31]1[C:9]([CH3:8])=[CH:10][C:26](=[O:27])[N:28]([CH3:33])[C:29]1=[O:30]

Participants

Reactant 3

HCID 6497Dimethyl Sulfate

HCID 122836-Methyluracil

HCID 160165837,9-dimethyl-6-(5-methylfuran-2-yl)-11-phenyl-5,6-dihydropyrimido[4',5':3,4]pyrrolo[1,2-a]quinoxaline-8,10(7H,9H)-dione2×

Product 1

HCID 260751,3,6-Trimethyl-2,4(1H,3H)-pyrimidinedione

Procedure

Synthesis of PPQ-102—Synthesis of PPQ-102 was achieved in six steps as illustrated in FIG. 2B. Commercially available 6-methyluracil 1 was methylated using dimethylsulfate to produce 1,3,6-trimethyluracil 2, which upon Friedel-Crafts acylation using zinc chloride as a catalyst yielded 5-benzoyl-1,3,6-trimethylpyrimidine-2,4(1H,3H)-dione 3 as a white powder. Bromination of 3 followed by reaction with N-(2-aminophenyl)acetamide generated amino-protected intermediate 5. The acetamido function of 5 was hydrolyzed and resultant intermediate 6 was cyclocondensed with 5-methylfurfural to yield yellowish-white racemic PPQ-102 7. Aromatic compound 8, which lacks a stereocenter, was prepared from 7 by oxidation with potassium permanganate.

Sources & evidence

ORD record: ord-3af435bfbebf40bc9f0a98e94c617241
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08609661B2

Reaction notes

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