Acetic Acid → Methyl 3-(6-bromo-4-oxoquinazolin-3(4H)-yl)-4-methylbenzoate

HRID 641946Notes

Reaction equation

HRID 641946 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([NH2:12])=[C:6]([CH:11]=1)[C:7](OC)=[O:8].[NH2:13][C:14]1[CH:15]=[C:16]([CH:21]=[CH:22][C:23]=1[CH3:24])[C:17]([O:19][CH3:20])=[O:18].[CH2:25](OC(OCC)OCC)C.C(O)(=O)C>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:11]=[C:6]2[C:5](=[CH:4][CH:3]=1)[N:12]=[CH:25][N:13]([C:14]1[CH:15]=[C:16]([CH:21]=[CH:22][C:23]=1[CH3:24])[C:17]([O:19][CH3:20])=[O:18])[C:7]2=[O:8]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 31214Ethyl orthoformateHCID 337778Methyl 3-amino-4-methylbenzoateHCID 736224Methyl 2-amino-5-bromobenzoate

Product 1

HCID 66919066Methyl 3-(6-bromo-4-oxoquinazolin-3(4H)-yl)-4-methylbenzoate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirred solution of methyl 5-bromo-2-aminobenzoate (10.0 g) and methyl 3-amino-4-methylbenzoate (7.90 g) in toluene (100 ml) at 50° C. were added triethylorthoformate (8.12 ml) and glacial acetic acid (2.50 ml). The mixture was heated to reflux for 16 hours. The alcohol by-products were distilled using Dean-stark conditions and the reaction cooled room temperature. The resultant solid was collected by filtration, washed with toluene (2×20 ml) and dried in vacuo at 40° C. to give the methyl 3-(6-bromo-4-oxoquinazolin-3(4H)-yl)-4-methylbenzoate as a white solid (13.1 g); NMR Spectrum: (DMSOd6) 2.16 (s, 3H), 3.85 (s, 3H), 7.60 (d, 1H), 7.71 (d, 1H), 8.01 (m, 3H), 8.26 (s, 1H), 8.34 (s, 1H); Mass Spectrum: M+H+ 373.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 16 hours
  3. distillationThe alcohol by-products were distilled
  4. filtrationThe resultant solid was collected by filtration
  5. washwashed with toluene (2×20 ml)
  6. customdried in vacuo at 40° C.

Sources & evidence

ORD record
ord-467b3c847ca6460ba09159b3819d8157
Source dataset
uspto-grants-2010_04
Patent number
US07696215B2

Reaction notes

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