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 vacuo, 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. 1H NMR (400 MHz, CDCl3) δ ppm 2392-2.94 (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 vacuo
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-5e710f735ca4465fb70907534c333299

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08314111B2