Benzenamine hydrochloride (1:1) → 5-(2-Isopropyl-4-methoxy-5-nitro-phenoxy)-pyrimidine-2,4-diamine

Temperature

100 °C

A mixture of (2-isopropyl-4-methoxy-5-nitro-phenoxy)-acetonitrile (8.785 g, 35.5 mmol) and Brederick's reagent (14.6 mL, 70.9 mmol) was warmed to 100° C. After 45 min the mixture was evaporated under reduced pressure (50° C., 50 mtorr) to give an orange solid. The solid was added to a solution of aniline hydrochloride (9.19 g, 70.9 mmol) in 150 mL of EtOH. The mixture was warmed to reflux. After 16 hr additional aniline hydrochloride (4.596 g, 35.5 mmol) was added mixture was continued at reflux for 4 h. The solution was concentrated in vacuo and poured into H2O. The mixture was extracted with ethyl acetate, washed with H2O, washed with brine, dried over Na2SO4, and concentrated in vacuo to afford a yellow-green solid. This crude product was added to a mixture of 200 mL NMP and guanidine carbonate (17.70 g, 98 mmol) and warmed to 130° C. After 5 hours the mixture was cooled then poured onto 2 l of an ice/H2O mixture. The resulting precipitate was filtered, washed with H2O and dried under vacuum (50° C.). The crude solid was recrystallized from EtOH to afford 5-(2-isopropyl-4-methoxy-5-nitro-phenoxy)-pyrimidine-2,4-diamine (8.14 g, 63%, 3 steps) as a yellow crystalline solid (solvated 1:1 with EtOH). (M+H)+=320.

1. customAfter 45 min the mixture was evaporated under reduced pressure (50° C., 50 mtorr)
2. customto give an orange solid
3. temperatureThe mixture was warmed to reflux
4. temperatureat reflux for 4 h
5. concentrationThe solution was concentrated in vacuo
6. additionpoured into H2O
7. extractionThe mixture was extracted with ethyl acetate
8. washwashed with H2O
9. washwashed with brine
10. dry with materialdried over Na2SO4
11. concentrationconcentrated in vacuo
12. customto afford a yellow-green solid
13. temperaturewarmed to 130° C
14. temperatureAfter 5 hours the mixture was cooled
15. filtrationThe resulting precipitate was filtered
16. washwashed with H2O
17. customdried under vacuum (50° C.)
18. customThe crude solid was recrystallized from EtOH

ORD record

ord-ce87052f091044a5ba3a9047c98ff7cb

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08524725B2