3-Methylenecyclobutanecarboxylic acid → N-((3-chloropyrazin-2-yl)methyl)-3-methylenecyclobutanecarboxamide

Temperature

60 °C

1,1′-Carbonyldiimidazole (CDI) (8.24 g, 50.81 mmol) and 3-methylenecyclobutanecarboxylic acid (5.70 g, 50.81 mmol) were dissolved in anhydrous THF (100 mL) and allowed to stir at 60° C. for 4 h. A solution of C-(3-Chloropyrazin-2-yl)methylamine bis-hydrochloride (10.0 g, 46.19 mmol) and diisopropylethylamine (DIPEA) (32.30 mL, 184.76 mmol) in anhydrous CH2Cl2 (150 mL) was added to the mixture and the reaction was allowed to stir at rt for 24 h. The mixture was concentrated in vacua, the residue dissolved in EtOAc and the resulting solution washed with saturated NaHCO3 (aq.) water H2O and Brine. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to afford crude product, which was purified by chromatography over silica gel eluting with 50-70% EtOAc/hexane to yield desired product. 1 H NMR (400 MHz, CDCl3) δ ppm 2.92-2.94 (2 H, m), 3.05-3.14 (2 H, m), 4.60 (2 H, d, J=4.24 Hz), 4.80-4.84 (2 H, m), 6.75 (1 H, brs), 8.33 (1 H, d, J=4.22 Hz) and 8.45 (1 H, d, J=2.54 Hz). MS (ES+): m/z 238 and 240 [MH+].

1. stirringto stir at rt for 24 h
2. concentrationThe mixture was concentrated in vacua
3. dissolutionthe residue dissolved in EtOAc
4. washthe resulting solution washed with saturated NaHCO3 (aq.) water H2O and Brine
5. dry with materialThe combined organic layers were dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customto afford crude product, which
9. customwas purified by chromatography over silica gel eluting with 50-70% EtOAc/hexane

ORD record

ord-df3258bc2a8149f4b800ef3f9de5d02d

Source dataset

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07943767B2