Acetanthranil → HCID 68282563, compound

HRID 1192748Notes

Reaction equation

HRID 1192748 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([C:8]#[C:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[NH2:16].[CH3:17][C:18]1[O:19][C:20](=O)[C:21]2[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=2[N:23]=1>C(O)(=O)C>[CH3:17][C:18]1[N:16]([C:3]2[CH:4]=[CH:5][C:6]([C:8]#[C:9][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)=[CH:7][C:2]=2[CH3:1])[C:20](=[O:19])[C:21]2[C:22](=[CH:24][CH:25]=[CH:26][CH:27]=2)[N:23]=1

Participants

4

Reactant 2

HCID 68236AcetanthranilHCID 68283007HCID 68283007, compound

Product 1

HCID 68282563HCID 68282563, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

4-iodo-2-methylbenzenamine 24 (233 mg, 1 mmol) on reaction with ethynyl benzene (25a, 102 mg, 1 mmol) by employing Sonagashira coupling conditions using Pd(PPh3)4 (69.3 mg, 0.06 equiv) as catalyst, CuI (22.8 mg, 0.12 equiv) as cocatalyst, butyl amine (261 mg, 3 equiv) as base and ether as solvent and kept the reaction for 6 h. After completion of the reaction as indicated by TLC and the reaction mixture is extracted into ether (4×25 mL) from the aqueous layer and concentrated in vacuo. The compound was further purified by column chromatography using 60-120 silica gel (ethyl acetate/hexane, 1:9) to obtain 2-methyl-4-(phenylethynyl)benzenamine compounds (26a) as pure product. Anthranilic acid (27, 137 mg, 1 mmol) on reaction with acetic anhydride at 150° C. and reflux for 30 min, after completion of reaction aqueous sodium bicarbonate solution is added and extracted in ethyl acetate (4×25 mL) from the aqueous layer and concentrated in vacuo afforded 2-methyl 4H-benzo[d][1,3]oxazin-4-one compound (28) as pure product. To a stirred solution of 2-methyl-4-(phenylethynyl)benzenamine (26a, 207 mg, 1 mmol) with 2-methyl-4H-benzo[d][1,3]oxazin-4-one (28, 161 mg, 1 mmol) in acetic acid and reflux for 8 h. After completion of the reaction as indicated by TLC, the reaction mixture was quenched with NaHCO3 and extracted in ethyl acetate (4×25 mL) from the ice cold aqueous layer and dried over anhydrous Na2SO4 afforded 2-methyl-3-(2-methyl-4-(phenylethynyl)phenyl)quinazolin-4(3H)-one (29a). Reaction of 2-methyl-3-(2-methyl-4-(phenylethynyl)phenyl)quinazolin-4(3H)-one (29a, 350 mg, 1 mmol) with 2,5-dihydroxy benzaldehyde (30c, 138 mg, 1 mmol) was taken in acetic acid Then the resulting mixture was stirred under reflux conditions for 8 h and then the reaction mixture was quenched with NaHCO3 and extracted in ethyl acetate (4×25 mL) from the ice cold aqueous layer and dried over anhydrous Na2SO4. The resulting product (4c) was purified by column chromatography employing EtOAc/Hexane as an eluent.

Workup

  1. customAfter completion of the reaction
  2. customthe reaction mixture was quenched with NaHCO3
  3. extractionextracted in ethyl acetate (4×25 mL) from the ice cold aqueous layer
  4. dry with materialdried over anhydrous Na2SO4

Sources & evidence

ORD record
ord-676ccef793664535b8b32d10c39490f8
Source dataset
uspto-grants-2014_03
Patent number
US08680272B2

Reaction notes

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