Réaction #657318

Équation de réaction

2-(4-fluorophenyl)-7-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine

N-(4-bromopyridin-2-yl)propanamide

Na2CO3

→

N-{4-[2-(4-fluorophenyl)-7-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl]pyridin-2-yl}propanamide

Rendement 23.5%

Solvants

1,4-dioxane

Conditions de réaction

Traitement

1. 1
   AutreThe reaction mixture is flushed for 5 mins with argon
2. 2
   Autresealed
3. 3
   TempératureAfter cooling
4. 4
   workup.ADDITIONthe reaction mixture is diluted with EtOAc
5. 5
   Lavagewashed with water
6. 6
   SéchageThe combined organic phase are dried over Na2SO4
7. 7
   Concentrationconcentrated in vacuo
8. 8
   AutreThe crude product is purified by silica gel chromatography (eluent cyclohexane/ethyl acetate)

Mode opératoire

150 mg of 2-(4-fluorophenyl)-7-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine (0.419 mmol, 1.1 eq.) and 87 mg of N-(4-bromopyridin-2-yl)propanamide (0.381 mmol, 1 eq.) are dissolved in 1.5 ml of 1,4-dioxane. To this solution are added 22 mg of bis(tricyclohexylphosphine)-palladium(II)dichloride (0.03 mmol, 0.08 eq) and a aqueous solution of Na2CO3 (5 eq, 0.952 ml). The reaction mixture is flushed for 5 mins with argon and then sealed. Next the mixture is heated for 15 mins at 120° C. in the microwave (CEM Explorer). After cooling, the reaction mixture is diluted with EtOAc and washed with water. The combined organic phase are dried over Na2SO4 and concentrated in vacuo. The crude product is purified by silica gel chromatography (eluent cyclohexane/ethyl acetate). 34 mg (21%) of N-{4-[2-(4-fluorophenyl)-7-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl]pyridin-2-yl}propanamide are obtained.

Source