Hydrochloric Acid → 3-[3-[[(1R,2R)-3-hydroxy-2-methyl-1-phenylpropyl]amino]-2-oxo-1(2H)-pyrazinyl]-4-methyl-benzoic acid, methyl ester

温度

50 °C

A mixture of (R)—N-[(1R,2R)-3-[[(1,1-dimethylethyl)diphenylsilyl]oxy]-2-methyl-1-phenylpropyl]-2-methyl-2-propanesulfinamide (Example 136b, 5.2 g), methanol (25 mL) and a solution of hydrogen chloride in 1,4-dioxane (4M, 25 mL) was stirred at 50° C. for 7 h and left at room temperature for 70 h. The mixture was concentrated in vacuo and the residue was washed with ether to give the crude amine hydrochloride (2.0 g). 3-(3,5-Dibromo-2-oxo-2H-pyrazin-1-yl)-4-methyl-benzoic acid, methyl ester (Example 1b, 3.5 g) was added followed by N,N-diisopropylethylamine (4 mL) and tetrahydrofuran (50 mL). The mixture was stirred at 50° C. for 24 h. After cooling to room temperature, the mixture was diluted with ethyl acetate (200 mL) and washed with sat. aqueous NaHCO3. The organic phase was dried (Na2SO4), filtered and concentrated in vacuo. Ethanol (50 mL) was added under nitrogen atmosphere followed by wet palladium on carbon (10%, 227 mg), ammonium formate (3 g) and N,N-diisopropylethylamine (2 mL). The mixture was stirred at 70° C. for 2 h, cooled to room temperature, filtered through a pad of Celite and concentrated in vacuo. The residue was diluted with ethyl acetate (200 mL) and washed with water. The organic phase was dried (Na2SO4), filtered and concentrated in vacuo to give the subtitle compound (3.5 g).

1. concentrationThe mixture was concentrated in vacuo
2. washthe residue was washed with ether
3. customto give the crude amine hydrochloride (2.0 g)
4. temperatureAfter cooling to room temperature
5. washwashed with sat. aqueous NaHCO3
6. dry with materialThe organic phase was dried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. additionEthanol (50 mL) was added under nitrogen atmosphere
10. stirringThe mixture was stirred at 70° C. for 2 h
11. temperaturecooled to room temperature
12. filtrationfiltered through a pad of Celite
13. concentrationconcentrated in vacuo
14. additionThe residue was diluted with ethyl acetate (200 mL)
15. washwashed with water
16. dry with materialThe organic phase was dried (Na2SO4)
17. filtrationfiltered
18. concentrationconcentrated in vacuo

ORDレコード

ord-5e634e1792f148f680baa6e6d7580ebd

出典データセット

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08299246B2