2-Bromo-3a,5,6,6a-tetrahydro-furo[2,3-c]pyrrol-4-one → 2-[8-(4-Morpholin-4-yl-phenylamino)-imidazo[1,2-a]pyrazin5-yl]-5,6-dihydro-furo[2,3-c]pyrrol-4-one

Participants

Reaction Steps

In the same way as described for Compound 212, step 3 using (4-morpholin-4-yl-phenyl)-(5-tributylstannanyl-imidazo[1,2-a]pyrazin-8-yl)-carbamic acid tert-butyl ester (255 mg, 0.373 mmol), 2-bromo-3a,5,6,6a-tetrahydro-furo[2,3-c]pyrrol-4-one (50 mg, 0.249 mmol) and Pd(PPh3)4 (29 mg, 0.0249 mmol) in DMF (3 mL). The reaction mixture is concentrated in vacuo and the residue dissolved in 1:1 DCM:TFA (drop of H2O) and stirred at room temperature for 3 hours. The mixture is partitioned between ethyl acetate and sat. NaHCO3 and the aqueous layer is extracted with ethyl acetate (3×). The organic layers are combined, dried over MgSO4, filtered and concentrated in vacuo. The residue is purified by silica gel column chromatography eluting with DCM followed by a 97:3 mixture DCM:NH3 (7M in MeOH). The fractions containing the desired compound are concentrated in vacuo to give a solid which is triturated with diethyl ether to afford the title compound (66.3 mg, 64%). Conversion of the compound into the mesylate salt using 1M MsOH (0.16 mL) affords the title product as a solid (69.3 mg, 87%). LCMS: Rt 2.52 min (99%), m/z (APCI) 417 (M+H)+, 1H-NMR (400 MHz, d6-DMSO) δ (ppm) 2.36 (3H, s, MsOH), 3.25 (4H, m), 3.84 (4H, m), 4.52 (2H, s), 7.18 (2H, br s), 7.40 (1H, s), 7.83 (1H, s), 7.90 (3H, m), 8.21 (1H, br s), 8.44 (1H, s), 10.25 (1H, br s).

Provenance & Evidence