2,4-Dihydroxybenzaldehyde → HCID 136344375, compound

HRID 1192753Notes

Reaction equation

HRID 1192753 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:18]=[CH:17][C:16]([N:19]3[C:28](=[O:29])[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[N:21]=[C:20]3[CH3:30])=[C:15](C)[CH:14]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[OH:32][C:33]1[CH:40]=[C:39]([OH:41])[CH:38]=[CH:37][C:34]=1[CH:35]=O>C(O)(=O)C>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:14]=[CH:15][C:16]([N:19]3[C:28](=[O:29])[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[N:21]=[C:20]3/[CH:30]=[CH:35]/[C:34]3[CH:37]=[CH:38][C:39]([OH:41])=[CH:40][C:33]=3[OH:32])=[CH:17][CH:18]=2)=[CH:7][CH:6]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

4

Reactant 2

HCID 72132,4-DihydroxybenzaldehydeHCID 68283139HCID 68283139, compound

Product 1

HCID 136344375HCID 136344375, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

4-iodo-2-methylbenzenamine 24 (233 mg, 1 mmol) on reaction with 1-tert-butyl-4-ethynylbenzene (25b, 158 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 4-((4-tert-butylphenyl)ethynyl)-2-methyl benzene amine (26b) 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 4-((4-tert-butylphenyl)ethynyl)-2-methylbenzenamine (26b, 263 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. 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 afforded 3-(4-((4-tert-butylphenyl)ethynyl)-2-methylphenyl)-2-methylquinazolin-4(3H)-one (29b). Reaction of 3-(4-((4-tert-butylphenyl)ethynyl)-2-methylphenyl)-2-methyl quinazolin-4(3H)-one (29b, 406 mg, 1 mmol) with 2,4-dihydroxybenzaldehyde (30d, 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 (5d) was purified by column chromatography employing EtOAc/Hexane as an eluent.

Workup

  1. customthe reaction mixture was quenched with NaHCO3
  2. extractionextracted in ethyl acetate (4×25 mL) from the ice cold aqueous layer
  3. dry with materialdried over anhydrous Na2SO4
  4. customThe resulting product (5d) was purified by column chromatography

Sources & evidence

ORD record
ord-87cb6f1f5451434fb3fc0549ad816ed2
Source dataset
uspto-grants-2014_03
Patent number
US08680272B2

Reaction notes

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