Ammonia methanol → 4-Aminopyrimidine

Temperature

0 °C

4,6-dichloro-5-nitro-2-methylmercaptopurine (1.0715 g, 4.502 mmol) was dissolved in 25 mL THF and cooled to 0° C. NH3/MeOH was added (3.5 Equiv) and the mixture was allowed to stir cold for 1 h. Aminoester (1.22 g, 4.37 mmol) was then added dropwise as a solution in 10 mL THF over 10-15 minutes, and the resulting mixture was allowed to warm to room temperature. After 3 h, the reaction was quenched with the addition of water, diluted with EtOAc and the pH was adjusted to ≧8 using solid K2CO3. The mixture was washed with water, washed with brine then dried with sodium sulfate and concentrated in vacuo. The crude product was then chromatographed on silica with a CH2Cl2 and 20% MeOH/CH2Cl2 gradient over 10-15 column volumes. Sometimes mixtures of 6-chloropyrimidine and 6-aminopyrimidine products are obtained (1.02 g) and are sequentially treated with excess NH3 in MeOH in THF over 45 minutes at room temperature and rechromatographed as above to give pure 6-aminopyrimidine product (716 mg). LCMS-ESI+: calc'd for C16H21N6O4S: 392.43 (M+H+). Found: 393.0 (M+H+).

1. temperatureto warm to room temperature
2. waitAfter 3 h
3. customthe reaction was quenched with the addition of water
4. additiondiluted with EtOAc
5. washThe mixture was washed with water
6. washwashed with brine
7. dry with materialthen dried with sodium sulfate
8. concentrationconcentrated in vacuo
9. customThe crude product was then chromatographed on silica with a CH2Cl2 and 20% MeOH/CH2Cl2 gradient over 10-15 column volumes

ORD record

ord-19e50929aa8348289f5b359f30849933

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09127006B2