Diisopropylethylamine → HCID 66561010, compound

Participants

Reaction Steps

To a stirred dark brownish solution of 5-(2,3-dihydro-1H-indol-5-yl)furo[2,3-d]pyrimidin-4-amine (360 mg, 1.43 mmol) and HATU (597 mg, 1.57 mmol, 1.1 equiv) in 3 mL of DMF was added DIEA (274 uL, 1.57 mmol, 1.1 equiv). To this mixture was added (2,5-difluorophenyl)acetic acid portionwise (246 mg total, 1.43 mmol, 1 equiv) over a 1 h period. The mixture was stirred for another 2 h and then added to 50 mL of ice water. The resulting suspension was filtered. The brownish cake was washed with water (2×10 mL) and then sucked under house vacuum for 20 h to give crude product (760 mg). This material was dissolved in 10% MeOH in DCM and absorbed onto a dryload cartridge. Purification was done on an SF25-60 g silica gel cartridge using gradient elution of 1% A to 55% A (A was a mixture of 3200 mL DCM, 800 mL of MeOH and 80 mL of conc NH4OH). The desired product eluted from 29-32%. Each fraction was checked by LCMS and the 2 pure fractions were combined with impure product from a previous run and concentrated in vacuo. The residue was dissolved in 10% MeOH in CHCl3, and filtered The filtrate was concentrated in vacuo. The residue was taken up in 1.5 mL of CHCl3, and MTBE (1 mL) and hexane (7 mL) were added to give a suspension. Which was filtered. The cake was washed with hexane (2×4 mL) and then dried under vacuum at 65° C. for 18 h to afford 5-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}furo[2, 3-d]pyrimidin-4-amine (295 mg) as an off-white solid. NMR, LCMS and HPLC showed this sample was pure. LC-MS (ES) m/z=407 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.28 (t, J=8.6 Hz, 2H), 3.96 (s, 3H), 4.30 (t, J=8.5 Hz, 2H), 7.13-7.28 (m, 3H), 7.30 (d, J=9.1 Hz, 1H), 7.40 (s, 1H), 7.93 (s, 1H), 8.12 (d, J=8.3 Hz, 1H), 8.25 (s, 1H), NH2 protons are not visible.

Provenance & Evidence