Acetic Acid → HCID 11245005, compound

HRID 2354200Notes

Reaction equation

HRID 2354200 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][C:3]=1[C:4]([OH:6])=O.[CH:13](OC)(OC)OC.C(O)(=O)C.[NH2:24][C:25]1[CH:26]=[C:27]([CH:34]=[CH:35][C:36]=1[CH3:37])[C:28]([NH:30][CH:31]1[CH2:33][CH2:32]1)=[O:29]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH:31]1([NH:30][C:28](=[O:29])[C:27]2[CH:34]=[CH:35][C:36]([CH3:37])=[C:25]([N:24]3[C:4](=[O:6])[C:3]4[C:2](=[CH:10][CH:9]=[C:8]([O:11][CH3:12])[CH:7]=4)[N:1]=[CH:13]3)[CH:26]=2)[CH2:32][CH2:33]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 9005Trimethyl orthoformateHCID 2779305-Methoxyanthranilic acidHCID 119838543-amino-N-cyclopropyl-4-methylbenzamide

Product 1

HCID 11245005HCID 11245005, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A stirred mixture of 2-amino-5-methoxybenzoic acid (10 g), trimethyl orthoformate (13.1 ml), and acetic acid (0.34 ml) in toluene (240 ml) was heated under reflux for 6 hours. 3-Amino-N-cyclopropyl-4-methylbenzamide (10.23 g) was added to the reaction mixture and stirring continued at reflux for 16 hours. The reaction mixture was allowed to cool and then was diluted with ethyl acetate. The organic solution was then washed with 1N HCl solution, 2N NaOH solution (×2), brine, dried (magnesium sulfate), and concentrated to a cream coloured foam/solid. Recrystallisation from ethyl acetate gave N-cyclopropyl-3-(6-methoxy-4-oxoquinazolin-3(4H)-yl)-4-methylbenzamide (AZ12239719) (11.33 g) as a white solid; NMR Spectrum: (DMSOd6) 0.62 (m, 2H), 0.75 (m, 2H), 2.19 (s, 3H), 2.90 (m, 1H), 3.95 (s, 3H), 7.56 (m, 2H), 7.63 (s, 1H), 7.78 (d, 1H), 7.89 (s, 1H), 7.95 (d, 1H), 8.23 (s, 1H), 8.48 (d, 1H); Mass Spectrum: M+H+ 350. B) To a solution of N-Cyclopropyl-3-(6-methoxy-4-oxoquinazolin-3(4H)-yl)-4-methylbenzamide (4.62 g) in methylene chloride (90 ml) was added 1M boron tribromide in methylene chloride (53 ml) and stirred for 20 hours. The reaction was quenched with water and then diluted with 2N NaOH solution until the solid dissolved. The aqueous layer was washed with methylene chloride (2×) and then acidified to pH 1 with 2N HCl solution and extracted with ethyl acetate (3×). The combined organic extracts were concentrated and the solid was dried by azeotropic removal of water using toluene to yield N-cyclopropyl-3-(6-hydroxy-4-oxoquinazolin-3(4H)-yl)-4-methylbenzamide (AZ12266450) (3.06 g) as a white solid; NMR Spectrum: (DMSOd6) 0.55 (m, 2H), 0.70 (m, 2H), 2.12 (s, 3H), 2.85 (m, 1H), 7.35 (d, 1H), 7.50 (s, 1H), 7.52 (d, 1H), 7.66 (d, 1H), 7.82 (s, 1H), 7.90 (d, 1H), 8.11 (s, 1H), 8.42 (d, 1H), 10.20 (broad s, 1H); Mass Spectrum: M+H+ 336.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 6 hours
  3. temperatureat reflux for 16 hours
  4. temperatureto cool
  5. washThe organic solution was then washed with 1N HCl solution, 2N NaOH solution (×2), brine
  6. dry with materialdried (magnesium sulfate)
  7. concentrationconcentrated to a cream
  8. customRecrystallisation from ethyl acetate

Sources & evidence

ORD record
ord-e5e096409c7c4b1d90895e5297410f0a
Source dataset
uspto-grants-2010_07
Patent number
US07750154B2

Reaction notes

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