Triethylamine → Methyl 2-(4-methylpiperazin-1-yl)pyrimidine-5-carboxylate

Temperature

0 °C

2-Chloropyrimidine 5-carboxylic acid (100 mg, 0.631 mmol, 1 eq) was suspended in a mixture of toluene (3 ml) and methanol (0.8 ml) under nitrogen and cooled in an ice-bath. Trimethylsilyldiazomethane (2M solution in hexanes, 0.347 ml, 0.694 mmol, 1.1 eq) was added dropwise. The solution was stirred at 0° C. for 10 min, then allowed to warm to room temperature and stirred for a further 1 h. 1-Methylpiperazine (70 μl, 0.631 mmol, 1 eq) and triethylamine (88 μl, 0.631 mmol, 1 eq) were added dropwise and stirring continued at room temperature for 2 h. The solvent was evaporated and the residue was taken up in ethyl acetate (20 ml) and water (15 ml). The layers were separated and the aqueous extracted with further portions of ethyl acetate (2×10 ml). The combined extracts were dried over MgSO4, filtered and evaporated. The reaction was repeated as above and the extracts combined with those above to afford methyl 2-(4-methylpiperazin-1-yl)pyrimidine-5-carboxylate as a gummy yellow solid (76 mg, 25% yield).

1. temperaturecooled in an ice-bath
2. temperatureto warm to room temperature
3. stirringstirred for a further 1 h
4. stirringstirring
5. waitcontinued at room temperature for 2 h
6. customThe solvent was evaporated
7. customThe layers were separated
8. extractionthe aqueous extracted with further portions of ethyl acetate (2×10 ml)
9. dry with materialThe combined extracts were dried over MgSO4
10. filtrationfiltered
11. customevaporated

ORD record

ord-d88f9ce2275d4968ba5c8e75013a906e

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08129391B2