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

Temperature

90 °C

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 hr, 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, tr=13.5 min) gave the title compound (348 mg, 1.320 mmol, 79% yield) as a yellow solid. ESI MS (M+H)+=262.0.

1. customcap
2. temperatureto cool to room temperature
3. filtrationThe reaction mixture was filtered through a disposable fritted funnel
4. washthe filter cake washed with EtOAc
5. additionThe filtrate was diluted with H2O
6. customthe layers were separated
7. washThe organic phase was washed with H2O (2×)
8. extractionThe combined aqueous phases were back-extracted with EtOAc (3×)
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated
12. customto afford an orange residue
13. customto be chromatographed
14. customPurification of the crude material by silica gel chromatography
15. customan ISCO machine (40 g column, 40 mL/min, 20-70% EtOAc in hexanes over 19 min, tr=13.5 min)

ORD record

ord-d8edd6850e374b70a4552a29a30992e9

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09242967B2