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

温度

100 °C

A mixture of (2-Isopropyl-4-methoxy-5-thiazol-4-yl-phenoxy)-acetonitrile (0.27 g, 0.94 mmol) and Brederick's reagent (0.35 g, 2.01 mmol) was heated at 100° C. for 2 hrs. Excess Brederick's reagent was removed under reduced pressure. The residue was dissolved in anhydrous EtOH (10 ml) and aniline HCl (0.38 g, 2.93 mmol) was added. The reaction mixture was heated at 80° C. for 18 hrs and partitioned between EtOAc and water. The combined organic extracts were dried over Na2SO4, filtered and concentrated. Guanidine carbonate (0.27 g, 1.49 mmol) and NMP (10 ml) were added and heated to 120° C. for 10 hrs. The reaction mixture was poured into water and extracted into EtOAc. The combined organic extracts were dried over Na2SO4, filtered and concentrated. Flash chromatography on silica (3% MeOH in methylene chloride with 0.1% NH4OH) gave 5-(2-Isopropyl-4-methoxy-5-thiazol-4-yl-phenoxy)-pyrimidine-2,4-diamine (0.15 g, 68%) as a solid. (M+H)=358.

1. customExcess Brederick's reagent was removed under reduced pressure
2. dissolutionThe residue was dissolved in anhydrous EtOH (10 ml)
3. temperatureThe reaction mixture was heated at 80° C. for 18 hrs
4. custompartitioned between EtOAc and water
5. dry with materialThe combined organic extracts were dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. temperatureheated to 120° C. for 10 hrs
9. extractionextracted into EtOAc
10. dry with materialThe combined organic extracts were dried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated

ORDレコード

ord-8c06519b6f364e26b61c9ee879ec780f

出典データセット

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08524725B2