反应详情

温度

90 °C

4-Fluorobenzonitrile (5 g, 41 mmol, 1 eq.) and 35 mL of dimethylformamide are placed in a 100 mL round-bottomed flask. N-Methylhomopiperazine (5.18 g, 45 mmol, 1.1 eq.) is added to this solution. The solution is heated at a temperature in the region of 90° C. for 36 hours and the solvent is then evaporated to dryness. The residue is diluted with 150 mL of ethyl acetate and 30 mL of water. The aqueous phase is extracted with ethyl acetate and the combined organic phases are dried over magnesium sulfate. After evaporation, the residual oil is purified by chromatography on a column of silica gel, eluting with a 0-10% methanol/dichloromethane gradient (Rf=0.2, 10/90 methanol/dichloromethane (v/v)). The 4-(4-methyl[1,4]diazepan-1-yl)benzonitrile (yellow solid) is placed directly in a mixture of 20 mL of 98% sulfuric acid and 2 mL of water. This orange solution is heated at a temperature in the region of 100° C. for 18 hours, and then cooled and hydrolyzed by pouring it onto ice. The pH is adjusted to 9-10 with sodium hydroxide pellets. The yellow precipitate obtained is filtered off and washed thoroughly with water and then dried under vacuum. 4-(4-Methyl[1,4]diazepan-1-yl)benzamide (3.7 g, 38%) is thus obtained in the form of a yellow solid, which is used directly in the following step.

1. customthe solvent is then evaporated to dryness
2. additionThe residue is diluted with 150 mL of ethyl acetate and 30 mL of water
3. extractionThe aqueous phase is extracted with ethyl acetate
4. dry with materialthe combined organic phases are dried over magnesium sulfate
5. customAfter evaporation
6. customthe residual oil is purified by chromatography on a column of silica gel
7. washeluting with a 0-10% methanol/dichloromethane gradient (Rf=0.2, 10/90 methanol/dichloromethane (v/v))
8. additionThe 4-(4-methyl[1,4]diazepan-1-yl)benzonitrile (yellow solid) is placed directly in a mixture of 20 mL of 98% sulfuric acid and 2 mL of water
9. temperatureThis orange solution is heated at a temperature in the region of 100° C. for 18 hours
10. temperaturecooled
11. additionhydrolyzed by pouring it onto ice
12. customThe yellow precipitate obtained
13. filtrationis filtered off
14. washwashed thoroughly with water
15. customdried under vacuum