o-Aminoacetanilide → 7,9-dimethyl-6-(5-methylfuran-2-yl)-11-phenyl-5,6-dihydropyrimido[4',5':3,4]pyrrolo[1,2-a]quinoxaline-8,10(7H,9H)-dione

HRID 1912351Notes

Reaction equation

HRID 1912351 reaction equation
[C:1]([C:9]1[C:10](=[O:19])[N:11]([CH3:18])[C:12](=[O:17])[N:13]([CH3:16])[C:14]=1[CH3:15])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[NH:27][C:28](=O)[CH3:29].CC1[O:38][C:35]([CH:36]=O)=[CH:34][CH:33]=1>[Cl-].[Zn+2].[Cl-]>[CH3:36][C:35]1[O:38][C:29]([CH:28]2[NH:27][C:22]3[C:21](=[CH:26][CH:25]=[CH:24][CH:23]=3)[N:20]3[C:15]2=[C:14]2[N:13]([CH3:16])[C:12](=[O:17])[N:11]([CH3:18])[C:10](=[O:19])[C:9]2=[C:1]3[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:33][CH:34]=1

Participants

5

Reactant 3

HCID 11149o-AminoacetanilideHCID 120975-MethylfurfuralHCID 8023085-benzoyl-1,3,6-trimethyl-2,4(1H,3H)-Pyrimidinedione

Product 1

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)-dione

Reagents, catalysts & solvents 1

HCID 3007855ZincchlorideCatalyst

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-89ebf1a1fee749128b9ea1ee97f756e7
Source dataset
uspto-grants-2013_12
Patent number
US08609661B2

Reaction notes

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