2-Amino-6-nitro-benzoic acid → 2-methyl-5-nitro-4H-benzo[d][1,3]oxazin-4-one

HRID 1777260Notes

Reaction equation

HRID 1777260 reaction equation
N[C:2]1C=CC=C2[C:3]=1C(=O)N(C1CCC(=O)NC1=O)C(C)=N2.[NH2:22][C:23]1[CH:31]=[CH:30][CH:29]=[C:28]([N+:32]([O-:34])=[O:33])[C:24]=1[C:25]([OH:27])=[O:26]>C(O)(=O)C>[CH3:2][C:3]1[O:26][C:25](=[O:27])[C:24]2[C:28]([N+:32]([O-:34])=[O:33])=[CH:29][CH:30]=[CH:31][C:23]=2[N:22]=1

Participants

4

Reactant 2

HCID 957952-Amino-6-nitro-benzoic acidHCID 24967599Avadomide

Product 1

HCID 666429832-methyl-5-nitro-4H-benzo[d][1,3]oxazin-4-one

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

In one specific 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 presence 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 the molar ratio of the activated acetic acid versus 2-amino-6-nitrobenzoic acid is ranging from about 1 to about 10, from about 1 to about 5, from about 1.5 to about 5, or from about 1.5 to about 2.5; and wherein steps (a), (b), (c), and (d) are each as described herein elsewhere.

Workup

  1. customIn one specific embodiment, provided herein
  2. additionan enantiomer or a mixture of enantiomers

Sources & evidence

ORD record
ord-6571b2adde484da9802eeb74638357e5
Source dataset
uspto-grants-2016_02
Patent number
US09266858B2

Reaction notes

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