N-3-Bromopropylphthalimide → (R)-2-(3-(5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-1'-yl)propyl)isoindoline-1,3-dione

Participants

Reaction Conditions

Reaction Steps

A mixture of (R)-5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]dihydrochloride (15 mg, 0.035 mmol), 2-(3-bromopropyl)isoindoline-1,3-dione (13 mg, 0.049 mmol), DIEA (0.018 mL, 0.11 mmol) and DMF (0.5 mL) was heated at about 150° C. in microwave for about 30 min. After cooling, the reaction mixture was partitioned between EtOAc and water. The aqueous phase was extracted with EtOAc. The combined organic layers were washed with water and brine, dried and concentrated. The residue was purified by column chromatography (DCM:MeOH, 20:1) to give (R)-2-(3-(5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-yl)propyl)isoindoline-1,3-dione (12 mg, 63%). LCMS (APCI+) m/z 542, 544 [M+H]+; Rt=3.79 min.

Provenance & Evidence