Water → 2,5-Diamino-4,6-dichloropyrimidine

Temperatur

115 °C

2,5-Diamino-4,6-dihydroxypyrimidine hydrochloride (0.14 mol, 25 g) was filled into a dry reactor. Dry 1,2,3-trichloropropane (51.96 ml) was then added and the whole was stirred. Subsequently, tetra-methylammonium chloride (0.29 mol, 31.25 g) and then POCl3 (0.54-0.81 mol, 124.9−83.28 g, 50.6-75.9 ml) were added. The reaction was heated at reflux temperature (about 115° C.) for 24 h. The reaction was then cooled to below 50° C., ice water (24.44 mol, 440.44 g) was added and the whole was kept below 55° C. Subsequently, the reaction was adjusted to a pH of between 6.5 and 7.0 using 50% strength NaOH (3.12 mol, 124.92 g, 163.3 ml) and the temperature was kept below 55° C. The reaction was stirred at between 50 and 60° C. for 30 min. Tetrahydrofuran (3.7 mol, 267.0 g, 300 ml) was then added. In order to remove undesired material, the whole mixture was filtered through Celite and the filter cake was then washed with ethyl acetate (20.5 mol, 1806.58 g, 2002.86 ml) for subsequent extraction. The organic phase (tetrahydrofuran and ethyl acetate) was washed 3 times with water (5.57 mol, 100.32 g, 100.32 l), dried over NaHCO3 and filtered. Ethyl acetate was removed by vacuum distillation. Hexane (0.77 mol, 66.14 g, 100.36 ml) was then added to the residual organic material, and the whole was cooled to below 10° C., filtered and then dried at 50° C. in vacuo. The title product (0.09 mol, 15.71 g) was obtained as a slightly brownish solid, corresponding to a yield of about 65% based on 2,5-diamino-4,6-dihydroxypyrimidine employed.

1. temperatureThe reaction was heated
2. temperatureThe reaction was then cooled to below 50° C.
3. customwas kept below 55° C
4. customwas kept below 55° C
5. stirringThe reaction was stirred at between 50 and 60° C. for 30 min
6. customIn order to remove undesired material
7. filtrationthe whole mixture was filtered through Celite
8. dry with materialdried over NaHCO3
9. filtrationfiltered
10. customEthyl acetate was removed by vacuum distillation
11. temperaturethe whole was cooled to below 10° C.
12. filtrationfiltered
13. customdried at 50° C. in vacuo

ORD-Eintrag

ord-9740d0888f804f079cbb427cdd97d183

Quelldatensatz

uspto-grants-2004_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06716981B2