Reaction #1069505

Reaction equation

5-methyl-5H-pyrido[3,4-f]pyrrolo[1,2-b][1,2,5]triazepine

4-chloro-1-methyl piperidine

magnesium

ammonium chloride

→

10,11-dihydro-5-methyl-10-[(1-methyl)piperidin-4-yl]-5H-pyrido[3,4-f]pyrrolo[1,2-b][1,2,5]triazepine

Yield 20.8%

Solvents

tetrahydrofuran

tetrahydrofuran

Conditions

Workup

1. 1
   Extractionextracted with ethyl acetate (3×)
2. 2
   WashThe combined organics were washed with water (2×)
3. 3
   Dryingdried over anhydrous magnesium sulfate
4. 4
   Filtrationfiltered
5. 5
   Concentrationconcentrated
6. 6
   OtherThe resultant solid was purified by means of high pressure liquid chromatography (silica gel; elution with 50% methanol/dichloromethane)
7. 7
   OtherRecrystallization from ethyl acetate:methanol (20:1)

Procedure

To a warm Grignard reagent prepared from 7.2 g of 4-chloro-1-methyl piperidine and 1.4 g of magnesium metal in 50 ml of tetrahydrofuran was added a solution of 5.3 g of 5-methyl-5H-pyrido[3,4-f]pyrrolo[1,2-b][1,2,5]triazepine in 50 ml of tetrahydrofuran. The reaction mixture was stirred at ambient temperature for 15 minutes, added to an iced ammonium chloride solution and extracted with ethyl acetate (3×). The combined organics were washed with water (2×) followed by a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and concentrated. The resultant solid was purified by means of high pressure liquid chromatography (silica gel; elution with 50% methanol/dichloromethane). Recrystallization from ethyl acetate:methanol (20:1) afforded 1.65 g of 10,11-dihydro-5-methyl-10-[(1-methyl)piperidin-4-yl]-5H-pyrido[3,4-f]pyrrolo[1,2-b][1,2,5]triazepine, mp: 235°-238° C. (dec.).

Source