Cyclobutanecarboxylic acid → HCID 178484143, compound

Participants

Reaction Steps

CDI (227 mg, 1.40 mmol) was added to a solution of cyclobutanecarboxylic acid (CAS 3721-95-7, 140 mg, 1.40 mmol) in THF (3 mL). The mixture was stirred for 30 min, and a solution of Example 377, ({trans-3-[2,4-Dichloro-3-(pyrrolidin-1-ylmethyl)phenoxy]cyclobutyl}methyl)methylamine (400 mg, 1.165 mmol) in THF (1 mL) was added. The reaction mixture was stirred for 16 h at room temperature and evaporated. CHCl3 (5 mL), a saturated solution of K2CO3 (0.5 mL), and water (0.5 mL) were added to the residue under stirring. The layers were separated, and the aqueous one was subjected to extraction with chloroform. The combined extracts were dried and evaporated. The residue was purified by chromatography (silica gel, 63-100 μm, 1 g, CHCl3/MeOH 100:0→80:10). Fractions containing the target product were evaporated. The residue was dissolved in ether (1 mL), and 4M HCl/dioxane (0.3 mL) was added under stirring. The obtained mixture was evaporated and dried in vacuo to afford the title compound (455 mg, 84%) as a light-yellow amorphous solid. LCMS data: 424.1, 425.1, 426.1, 427.1 (M+H) (calculated for C22H30Cl2N2O2 425.4). 1H NMR-data (DMSO-d6): 10.5 (brs, 1H, NH+), 7.54, 7.53 (2d, 1H, J=9 Hz, Ar—H); 7.12, 7.09 (2d, 1H, J=9 Hz, Ar—H); 4.89-5.06 (m, 1H); 4.59 (s, 2H, CH2); 3.48-3.59 (m, 2H), 3.19-3.48 (m, 5H); 2.77, 2.86 (2s, 3H, NCH3), 2.53-2.66 (m, 1H), 1.82-2.33 (m, 13H); 1.66-1.79 (m, 1H).

Provenance & Evidence