Hydrochloric Acid → HCID 86712637, compound

Participants

Reaction Steps

HOBt (15 mg, 0.11 mmol), EDCl.HCl (21 mg, 0.11 mmol) and DIPEA (72 μL, 0.41 mmol) were added to a solution of 2-(2-(2-(2-((4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)amino)-5-methylpyrimidin-4-yl)ethyl)phenyl)acetic acid (A9) (44 mg, 0.083 mmol) in dry DMF (10 mL) under an atmosphere of nitrogen. After 10 minutes ammonium carbonate (40 mg, 0.41 mmol) was added and the resulting mixture was stirred at room temperature for 18 hours. A solution of HOBt (15 mg, 0.11 mmol), EDCl.HCl (21 mg, 0.11 mmol) and DIPEA in DMF (3 mL) was then added and after 10 minutes ammonium carbonate (40 mg, 0.41 mmol) was added in one portion. The resulting mixture was stirred at 26° C. for a further 24 hours before the volatiles were removed in vacuo and the residue partitioned between EtOAc (65 mL) and saturated NaHCO3 (65 mL). The aqueous layer was extracted with EtOAc (2×50 mL) then the combined organics were washed with brine (50 mL) and dried over Na2SO4. After filtration the solvent was removed in vacuo to afford a pale yellow solid which was adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C. then 0-100% MeOH in EtOAc). After removing the solvent in vacuo the resulting residue was taken up in EtOAc, filtered through cotton wool and the filtrate evaporated to dryness to give the title compound A10 as a light brown solid (28 mg, 64%); 1H NMR (400 MHz, CDCl3) δ 8.05 (s, 1H), 7.47-7.41 (m, 2H), 7.25-7.17 (m, 4H), 7.13 (s, 1H), 6.93-6.88 (m, 2H), 5.59 (s, 1H), 5.53 (s, 1H), 3.65 (s, 2H), 3.61-3.55 (m, 4H), 3.10-3.01 (m, 6H), 2.92-2.88 (m, 2H), 2.08 (s, 3H), 1.48 (s, 9H). LCMS-A: rt 5.525 min; m/z 531.2 [M+H]+

Provenance & Evidence