Cesium carbonate → N-Cyclopropyl-5-iodopyrimidin-4-amine

Participants

Reaction Conditions

Reaction Steps

To a vial containing a solution of 4-chloro-5-iodopyrimidine (0.400 g, 1.664 mmol) in DMF (Volume: 2.67 ml) was added cyclopropanamine (0.461 ml, 6.65 mmol) followed by cesium carbonate (1.084 g, 3.33 mmol). The vial was sealed with a Teflon cap and heated at 90° C. for 3 h, then allowed to cool to room temperature. The reaction mixture was filtered through a disposable fritted funnel and the filter cake washed with EtOAc. The filtrate was diluted with H2O and the layers were separated. The organic phase was washed with H2O (2×). The combined aqueous phases were back-extracted with EtOAc (3×). All organics were combined, dried over Na2SO4, filtered, and concentrated to afford an orange residue. The crude material was dissolved in a minimal amount of CH2Cl2 to be chromatographed. Purification of the crude material by silica gel chromatography using an ISCO machine (40 g column, 40 mL/min, 20-70% EtOAc in hexanes over 19 min, ret. T=13.5 min) gave Intermediate 108A (348 mg, 1.320 mmol, 79% yield) as a yellow solid. MS (ESI): m/z=262.0 [M+H]+ HPLC Peak ret. T=1.47 minutes was product. (HPLC conditions: Column:Luna C18 4.6×30 mm 3 u A:10:90 H2O:ACN NH4OAc/B:10:90 H2O:ACN NH4OAc; 0%-95% B in 2 min; 4 mL/min flow).

Provenance & Evidence