3-Amino-2,6-piperidinedione → 3-(2-methyl-5-nitro-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione
Reaction equation
[O:1]=[C:2]1[CH:7]([N:8]2C(=O)C3C(=CC=CC=3NC=O)N=C2C)[CH2:6][CH2:5][C:4](=[O:23])[NH:3]1.[CH3:24][C:25]1O[C:27](=[O:38])[C:28]2[C:34]([N+:35]([O-:37])=[O:36])=[CH:33][CH:32]=[CH:31][C:29]=2[N:30]=1.NC1CCC(=O)NC1=O>>[CH3:24][C:25]1[N:8]([CH:7]2[CH2:6][CH2:5][C:4](=[O:23])[NH:3][C:2]2=[O:1])[C:27](=[O:38])[C:28]2[C:29](=[CH:31][CH:32]=[CH:33][C:34]=2[N+:35]([O-:37])=[O:36])[N:30]=1Participants
Procedure
In one particular embodiment, provided herein is a method for preparing 3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione, or an enantiomer or a mixture of enantiomers thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or polymorph thereof; comprising the steps of (a) reacting 2-amino-6-nitrobenzoic acid with an activated acetic acid in a solvent to form 2-methyl-5-nitro-4H-benzo[d][1,3]oxazin-4-one; (b) reacting 2-methyl-5-nitro-4H-benzo[d][1,3]oxazin-4-one with 3-aminopiperidine-2,6-dione or a salt thereof in a solvent in the present of a coupling reagent to form 3-(2-methyl-5-nitro-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione; (c) reducing 3-(2-methyl-5-nitro-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione in a solvent in the presence of formic acid via transfer hydrogenation to form N-(3-(2,6-dioxopiperidin-3-yl)-2-methyl-4-oxo-3,4-dihydroquinazolin-5-yl)formamide; and (d) hydrolyzing N-(3-(2,6-dioxopiperidin-3-yl)-2-methyl-4-oxo-3,4-dihydroquinazolin-5-yl)formamide in a solvent to form 3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione, or an enantiomer or a mixture of enantiomers thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or polymorph thereof; wherein steps (a), (b), (c), and (d) are each as described herein elsewhere.
Sources & evidence
- ORD record
- ord-77e5e0c38e6942c2849f848e7c21e606
- Source dataset
- uspto-grants-2016_02
- Patent number
- US09266858B2
Reaction notes
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