Piperazine → HCID 44253238, compound

Participants

Reaction Conditions

Reaction Steps

Lithium bis(trimethylsilyl)amide, (1.0M solution in tetrahydrofuran, 1.68 ml, 1.68 mmol) under an atmosphere of N2 was added to a solution of 2′-((4-bromophenyl)amino)spiro[cycloheptane-1,7′-pyrrolo[3,4-d]pyrimidin]-5′(6′H)-one (136) (0.217 g, 0.560 mmol), and piperazine (0.145 g, 1.68 mmol) in anhydrous toluene (3 ml). After degassing the solution with nitrogen, S-Phos (0.092 g, 0.224 mmol) and tris(dibenzylideneacetone)-dipalladium (0) (0.051 g, 0.056 mmol) were added and the reaction was heated at 100° C. for 2 hrs. Additional lithium bis(trimethylsilyl)amide, 1.0M solution in tetrahydrofuran (1.68 ml, 1.68 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.051 g, 0.056 mmol), and S-Phos were added (0.092 g, 0.224 mmol) and the reaction was heated at 100° C. for another 1 hr before it was cooled to 20° C. The reaction was quenched with methanol and concentrated under vacuum. The residue was triturated with DCM and solids removed by filtration. The filtrate was concentrated under vacuum and purified by preparative HPLC eluting with a gradient of 20% MeCN-60% MeCN/H2O/0.1% TFA. The fractions containing the product were combined and concentrated under vacuum. Trituration with methanol gave 2′4((4-(1-piperazinyl)phenyl)amino)spiro[cycloheptane-1,7′-pyrrolo[3,4-d]pyrimidin]-5′(6′H)-one (131) as a white solid (26 mg, crude). 1H NMR (500 MHz, DMSO-d6) δ ppm 10.02 (1H, s), 8.75 (1H, s), 8.73 (2H, br. s.), 8.62 (1H, s), 7.68 (2H, d, J=8.5 Hz), 6.99 (2H, d, J=9.2 Hz), 3.28-3.32 (4H, m), 3.21-3.28 (4H, m), 1.92-2.02 (2H, m), 1.77-1.86 (2H, m), 1.55-1.77 (8H, m); LCMS-ESI (POS), M/Z, M+1: Found 393.2.

Provenance & Evidence