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-diisopropylethylamine (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-diisopropylethylamine (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レコード

ord-22ab0d5d3ed24d62817430821a655b5f

出典データセット

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08163905B2