Cesium carbonate → 5-(4-(4-((3aR,6aR)-5-methylhexahydropyrrolo[3,4-b]pyrrol-1(2H)-yl)phenyl)piperazin-1-yl)picolinonitrile

Participants

Reaction Conditions

Reaction Steps

The product of Example 75A (78.0 mg, 0.27 mmole), 5-bromo-2-cyanopyridine (74.8 mg, 0.41 mmole), palladium acetate (2.5 mg, 0.011 mmole), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (19.0 mg, 0.037 mmole), cesium carbonate (142.1 mg, 0.44 mmole) and 3 ml of tetrahydrofuran were mixed under N2 in a Emrys process vial. The vial was sealed and heated in the microwave for 2 hours at 120° C. using the Emrys Creator. The mixture was diluted with water and extracted with dichloromethane (4×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to give the crude product which was purified by column chromatography (10% methanol and 1% ammonium hydroxide in dichloromethane) to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 8.36 (d, J=2.71 Hz, 1H) 7.53 (d, J=8.82 Hz, 1H) 7.13 (dd, J=8.82, 3.05 Hz, 1H) 6.86-6.98 (m, 2H) 6.50-6.65 (m, 2H) 4.06 (t, J=8.65 Hz, 1H) 3.44-3.59 (m, 5H) 3.11-3.24 (m, 5H) 2.88-3.02 (m, 1H) 2.56-2.72 (m, 4H) 2.33 (s, 3H) 2.06-2.24 (m, 1H) 1.83-2.01 (m, 1H). MS: (M+H)+=389.

Provenance & Evidence