2-Amino-3-methylbenzoic acid → 8-methyl-2,4-dihydro-1H-3,1-benzoxazine-2,4-dione

HRID 927288Notes

Reaction equation

HRID 927288 reaction equation
[NH2:1][C:2]1[C:10]([CH3:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].Cl[C:13](Cl)([O:15]C(=O)OC(Cl)(Cl)Cl)Cl>C1COCC1>[CH3:11][C:10]1[C:2]2[NH:1][C:13](=[O:15])[O:5][C:4](=[O:6])[C:3]=2[CH:7]=[CH:8][CH:9]=1

Participants

4

Reactant 2

HCID 781012-Amino-3-methylbenzoic acidHCID 94429Triphosgene

Product 1

HCID 27598708-methyl-2,4-dihydro-1H-3,1-benzoxazine-2,4-dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The compounds of this invention can be prepared as illustrated by the exemplary reaction in Scheme 3. Reaction of 2-amino-3-methylbenzoic acid with triphosgene in THF produced 8-methyl-1H-benzo[d][1,3]oxazine-2,4-dione, which was treated with tert-butylamine and DMAP in DMF to produce 2-amino-N-tert-butyl-3-methylbenzamide. Reaction of the benzamide with CDI in THF produced 3-tert-butyl-8-methylquinazoline-2,4(1H,3H)-dione, which was reacted with methyl 3-(bromomethyl)benzoate and MeONa in DMF, followed by treatment with hydrochloric acid aqueous solution, to produce 8-methyl-1-(3-carboxybenzyl)quinazoline-2,4(1H,3H)-dione. Coupling of the acid with 2-(piperazin-1-yl)pyrimidine in the presence of coupling agents, such as HATU and DIPEA in DMF, produced the targeted compound 8-methyl-1-(3-(4-(pyrimidin-2-yl)piperazine-1-carbonyl)benzyl)quinazoline-2,4(1H,3H)-dione.

Workup

  1. customThe compounds of this invention can be prepared
  2. customas illustrated by the exemplary reaction in Scheme 3

Sources & evidence

ORD record
ord-453191ff3dac49d18d816acc3105de22
Source dataset
uspto-grants-2016_03
Patent number
US09290460B2

Reaction notes

Loading…