Boron tribromide → HCID 11404895, compound

HRID 2354201Notes

Reaction equation

HRID 2354201 reaction equation
[CH:1]1([NH:4][C:5](=[O:26])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([N:13]3[C:22](=[O:23])[C:21]4[C:16](=[CH:17][CH:18]=[C:19]([O:24]C)[CH:20]=4)[N:15]=[CH:14]3)[CH:7]=2)[CH2:3][CH2:2]1.B(Br)(Br)Br>C(Cl)Cl>[CH:1]1([NH:4][C:5](=[O:26])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([N:13]3[C:22](=[O:23])[C:21]4[C:16](=[CH:17][CH:18]=[C:19]([OH:24])[CH:20]=4)[N:15]=[CH:14]3)[CH:7]=2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 11245005HCID 11245005, compound

Product 1

HCID 11404895HCID 11404895, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

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. customThe reaction was quenched with water
  2. additiondiluted with 2N NaOH solution until the solid
  3. dissolutiondissolved
  4. washThe aqueous layer was washed with methylene chloride (2×)
  5. extractionextracted with ethyl acetate (3×)
  6. concentrationThe combined organic extracts were concentrated
  7. dry with materialthe solid was dried by azeotropic removal of water

Sources & evidence

ORD record
ord-7b461b2e3da04547a916b8997aca6925
Source dataset
uspto-grants-2010_07
Patent number
US07750154B2

Reaction notes

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