Cyclopropylamine → N-Cyclopropyl-4-methyl-3-[2-oxo-3-[[(2S)-2-phenylpropyl]amino]-1(2H)-pyrazinyl]benzamide

A mixture of 3-(3,5-dibromo-2-oxo-2H-pyrazin-1-yl)-4-methyl-benzoic acid, methyl ester (Example 1b, 0.1 g), N,N-diisopropylethylamnie (0.1 mL), (S)-2-phenyl-1-propylamine (0.05 mL) and tetrahydrofuran (1 mL) was stirred at room temperature overnight. Cyclopropylamine (0.2 mL) was added followed by the addition of cyclopentylmagnesium bromide (2M in diethyl ether, 0.8 mL). The mixture was stirred for 10 min., quenched with sat. NH4Cl and extracted into ethyl acetate. The organic phase concentrated in vacuo. The residue was treated with ethanol (5 mL), wet 10% palladium on carbon (45 mg) was added followed by N,N-diisopropylethylamnie (0.1 mL) and ammonium formate (0.4 g). The mixture was stirred under nitrogen atmosphere at 70° C. for 30 min. The mixture was filtered through a pad of Celite and the filtrate concentrated in vacuo. Purification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent) afforded the title compound as a solid (64 mg).

1. stirringThe mixture was stirred for 10 min.
2. customquenched with sat. NH4Cl
3. extractionextracted into ethyl acetate
4. concentrationThe organic phase concentrated in vacuo
5. additionThe residue was treated with ethanol (5 mL), wet 10% palladium on carbon (45 mg)
6. additionwas added
7. stirringThe mixture was stirred under nitrogen atmosphere at 70° C. for 30 min
8. filtrationThe mixture was filtered through a pad of Celite
9. concentrationthe filtrate concentrated in vacuo
10. customPurification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent)

ORD record

ord-1aa98f456da84db0966df5bac3842004

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889692B2