Reaction #41239

Reaction equation

product

(3aR,6aR)-1-(4-Bromo-phenyl)-5-methyl-octahydro-pyrrolo[3,4-b]pyrrole

product

6-Piperazin-1-yl-nicotinonitrile

racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl

sodium tert-butoxide

→

title compound

(3aR,6aR)-6-{4-[4-(5-Methyl-hexahydro-pyrrolo[3,4-b]pyrrol-1-yl)-phenyl]-piperazin-1-yl}-nicotinonitrile

Solvents

water

toluene

Conditions

Workup

1. 1
   TemperatureThe mixture was cooled to room temperature
2. 2
   Extractionextracted with dichloromethane (5×)
3. 3
   DryingThe combined organics were dried over sodium sulfate
4. 4
   Filtrationfiltered
5. 5
   Concentrationconcentrated under reduced pressure
6. 6
   Otherpurified by chromatography (
7. 7
   Washeluting with a mixture of 5% methanol in dichloromethane)

Procedure

The product of Example 7C (281.2 mg, 1.0 mmole), the product of Example 48A (226 mg, 1.2 mmole), tris(dibenzylideneacetone)dipalladium (18.3 mg, 0.02 mmole), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (25.0 mg, 0.04 mmole) and sodium tert-butoxide (145 mg, 1.5 mmole) were dissolved in 5 ml of toluene and heated at 70° C. under N2 for 24 hours. The mixture was cooled to room temperature, diluted with water and extracted with dichloromethane (5×). The combined organics were dried over sodium sulfate, filtered, and concentrated under reduced pressure and purified by chromatography (eluting with a mixture of 5% methanol in dichloromethane) to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 8.43 (d, J=1.70 Hz, 1H) 7.62 (dd, J=8.98, 2.20 Hz, 1H) 6.92 (d, J=8.81 Hz, 2H) 6.64 (d, J=9.15 Hz, 1H) 6.56 (d, J=9.15 Hz, 2H) 4.01-4.15 (m, 1H) 3.79-3.88 (m, 4H) 3.45-3.55 (m, 1H) 3.14-3.23 (m, 1H) 3.08-3.14 (m, 4H) 2.97-3.04 (m, 1H) 2.55-2.75 (m, 4H) 2.36 (s, 3H) 2.09-2.22 (m, 1H) 1.92 (m, 1H); MS (M+H)+=389.

Source