تفاعل #731412

معادلة التفاعل

isocyanate

2-fluoroaniline

allyl magnesium bromide

6-fluoro-2-[4-(pyrrolidin-1-yl)-2-(1-methylpiperidin-4-yloxy)phenyl]-4H-3,1-benzoxazin-4-one

→

5-Fluoro-N-(2-fluorophenyl)-2-[2-(1-methylpiperidin-4-yloxy)-4-(pyrrolidin-1-yl)benzoylamino]benzamide

المذيبات

THF

diethyl ether

THF

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGThe reaction was stirred overnight at ambient temperature
2. 2
   تركيزconcentrated to dryness
3. 3
   workup.ADDITIONmixed with saturated aqueous NaHCO3 (1 mL) and CH2Cl2 (2 mL)
4. 4
   ترشيحThe mixture was filtered through a plug of diatomaceous earth
5. 5
   أخرىPurification
6. 6
   غسيلeluting with 1% MeOH in CHCl3

الإجراء التجريبي

A solution of 2-fluoroaniline (22.1 mg, 0.18 mmol) in dry THF (1 mL) was treated with a 1 M diethyl ether solution of allyl magnesium bromide (0.2 mL). The reaction was stirred for 5 minutes before adding 6-fluoro-2-[4-(pyrrolidin-1-yl)-2-(1-methylpiperidin-4-yloxy)phenyl]-4H-3,1-benzoxazin-4-one (25 mg, 0.06 mmol) in THF (1 mL). The reaction was stirred overnight at ambient temperature, concentrated to dryness and mixed with saturated aqueous NaHCO3 (1 mL) and CH2Cl2 (2 mL). The mixture was filtered through a plug of diatomaceous earth and treated with an isocyanate resin (methylisocyanate polystyrene HL, 0.360 mmol) overnight. Purification consisted of applying this mixture directly onto a column of silica and eluting with 1% MeOH in CHCl3.

المصدر