Propionic Acid → HCID 59605714, compound

Participants

Reaction Steps

To a solution of 2-{1-[2-(2-amino-3-fluorophenylamino)-9-methyl-6-morpholin-4-yl-9H-purin-8-ylmethyl]piperidin-4-yl}propan-2-ol (65 mg, 0.13 mmol), propionic acid (78 uL, 0.14 mmol) and DIPEA (49 uL, 0.29 mmol) in DMF (3 mL) was added HATU (59 mg, 0.16 mmol). The reaction mixture was stirred at room temperature for 18 hours. Propionic acid (78 uL, 0.14 mmol), DIPEA (49 uL, 0.29 mmol) and HATU (59 mg, 0.16 mmol) were added and the reaction mixture was stirred at room temperature for 2 days, then diluted with water and extracted with EtOAc. The organic layer was separated and washed with water, a saturated aqueous solution of sodium bicarbonate and brine, dried over Na2SO4, filtered and concentrated to give a red oil dissolved in acetic acid (2 mL). The mixture was stirred at 90° C. for 18 hours then concentrated under reduced pressure. The residue was azeotroped with toluene, then taken up in MeOH. The resulting solution was loaded onto an Isolute® SCX-2 cartridge (5 g). The cartridge was washed with MeOH and the desired product was eluted with 2M NH3 in MeOH. The solvents were removed and the residue was subjected to flash chromatography (Si—PCC, 0-20% MeOH in EtOAc) to give 485 (36 mg, 52%). LCMS (Method I): RT 3.18 min; [M+H]+ 537. 1H NMR (400 MHz, CHCl3-d): δ 7.78-7.75 (m, 1 H); 7.21-7.12 (m, 1 H); 6.97 (dd, J=10.3, 8.0 Hz, 1 H); 4.34 (m, 4 H); 3.90-3.84 (m, 7 H); 3.73 (s, 2 H); 3.35 (q, 7.5 Hz, 2 H); 2.97 (d, J=11.4 Hz, 2 H); 2.12 (m, 2 H); 1.77 (m, 2 H); 1.44 (t, J=7.5 Hz, 3 H); 1.44-1.28 (m, 4 H); 1.24-1.15 (m, 6 H)

Provenance & Evidence