反应详情

2'-Methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-carboxylic acid (EP 0533268A1) (77 mg, 0.26 mmol) was treated with thionyl chloride (5 ml) and the mixture heated under reflux under Ar for 1 hour, then concentrated in vacuo to afford a yellow solid. This was dissolved in dichloromethane (5 ml) and treated with a solution of 6-amino-3,4-dihydro-4-(2-dimethylaminoethyl)-3-methyl-2H-1,4-benzoxazine (D14, 61.7 mg, 0.26 mmol) and triethylamine (0.11 ml, 0.78 inmol) in dichloromethane (10 ml). The reaction mixture was stirred at room temperature under Ar for 24 hours, then washed with brine/saturated potassium carbonate solution (30 ml of a 1:1 solution). The organic layer was separated, dried (Na2SO4) and concentrated in vacuo to afford a brown oil. This was chromatographed on SiO2, eluting with 0-8% methanol/dichloromethane to afford the title compound as a light yellow oil (72.2 mg, 54%).

1. temperaturethe mixture heated
2. temperatureunder reflux under Ar for 1 hour
3. concentrationconcentrated in vacuo
4. customto afford a yellow solid
5. washwashed with brine/saturated potassium carbonate solution (30 ml of a 1:1 solution)
6. customThe organic layer was separated
7. dry with materialdried (Na2SO4)
8. concentrationconcentrated in vacuo
9. customto afford a brown oil
10. customThis was chromatographed on SiO2
11. washeluting with 0-8% methanol/dichloromethane