Tetrahydrofuran → N2-Cyclopropylpyrazine-2,3-diamine

Participants

Reaction Conditions

Reaction Steps

To a 250 mL round bottomed flask was added 2-amino-3-chloropyrazine (2.2204 g, 17.14 mmol, Synthetech, Inc.) and BrettPhos precatalyst (0.411 g, 0.514 mmol, Sigma-Aldrich Chemical Company, Inc.), and the reaction mixture were placed under vacuum. The round bottomed flask was flushed with argon. This process was repeated 3 times. Cyclopropylamine (1.803 ml, 25.7 mmol, Fluka Chemie GmbH) was added followed by a dropwise addition of lithium bis(trimethylsilyl)amide, 1.0 m solution in tetrahydrofuran (42.8 ml, 42.8 mmol, Sigma-Aldrich Chemical Company, Inc.). The reaction mixture was then heated to 45° C. for 2 h. The reaction mixture was then diluted with saturated NH4Cl and extracted with CH2Cl2. The organic extract was washed with water, saturated NaCl, dried over MgSO4, filtered and concentrated in vacuo. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage SNAP HP-silica gel column (50 g), eluting with a gradient of 10% to 60% Acetone in DCM, to provide the title compound (0.7993 g, 5.32 mmol, 31.1% yield). LCMS showed product peak at 0.629 min (m+1=151.1) with purity at 80-90%. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.31-0.38 (m, 2 H) 0.59-0.66 (m, 2 H) 2.64 (tq, J=6.85, 3.52 Hz, 1 H) 5.79 (s, 2 H) 6.25 (d, J=2.15 Hz, 1 H) 7.08 (d, J=3.13 Hz, 1 H) 7.20 (d, J=3.13 Hz, 1 H).

Provenance & Evidence