反応 #78164

反応方程式

phosphorus pentoxide

triethylamine hydrochloride

4-tert-butylaniline

4-(4-pyridylmethyl)-1(2H)-phthalazinone

→

title compound

1-(4-tert-Butylanilino)-4-(4-pyridylmethyl)phthalazine dihydrochloride

溶媒

dichloromethane

反応条件

後処理

1. 1
   ろ過filtered off from undissolved components
2. 2
   その他the filtrate evaporated in the RE
3. 3
   workup.ADDITIONa mixture of 20 ml water and 5 ml conc. ammonia
4. 4
   乾燥the organic phase dried over anhydrous sodium sulfate
5. 5
   ろ過filtered
6. 6
   その他evaporated under vacuum
7. 7
   workup.STIRRINGThe residue is then stirred with 10 ml acetonitrile
8. 8
   ろ過filtered off from some non-transformed 4-(4-pyridylmethyl)-1(2H)-phthalazinone
9. 9
   その他the filtrate evaporated under vacuum

実験手順

In the manner described in Example 45, a mixture of 1.80 g (12.68 mmol) phosphorus pentoxide, 1.73 g (12.6 mmol) triethylamine hydrochloride, 1.9 ml (12.5 mmol) 4-tert-butylaniline, and 1 g (4.2 mmol) 4-(4-pyridylmethyl)-1(2H)-phthalazinone is stirred for 4.5 h at 210° C. The frozen melt is then dissolved in dichloromethane using an ultrasonic bath, filtered off from undissolved components, and the filtrate evaporated in the RE. The oil-like residue is distributed between dichloromethane and a mixture of 20 ml water and 5 ml conc. ammonia, and the organic phase dried over anhydrous sodium sulfate, filtered and evaporated under vacuum. The residue is then stirred with 10 ml acetonitrile, filtered off from some non-transformed 4-(4-pyridylmethyl)-1(2H)-phthalazinone, and the filtrate evaporated under vacuum. Flash chromatography of the residue on silica gel with a particle size of 0.04-0.06 mm using a toluene/acetone mixture (7:3) yields a resin (free base of the title compound), which is dissolved in a mixture of 4 ml methanol and 1.5 ml of 3 N methanolic HCl. After evaporation under vacuum, recrystallization of the residue from methanol/ether, drying under HV (6 h, 80° C.), and equilibration for 16 h at 200° C. and in room atmosphere, title compound is obtained with a water content of 4.47%; m.p. 196-200° C.; ESI-MS: (M+H)+=369.

出典