5-Amino-2,3-dihydro-isoindol-1-one → 5-[(2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)amino]isoindolin-1-one

Participants

Reaction Conditions

Reaction Steps

2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl 4-methylbenzenesulfonate from step 1 of Example 5 (100 mg, 0.23 mmol) was dissolved in sulfolane and 5-aminoisoindolin-1-one (68 mg, 0.46 mmol) from step 3 of this example added. The mixture was at stirred 110° C. for 3 and at 120° C. for 2 hours. The mixture was cooled to RT, diluted with 4:1 water:saturated sodium bicarbonate (40 ml), extracted with EtOAc (3×30 ml), the organic fractions combined, washed with brine, dried over Na2SO4, filtered, the volatiles removed in vacuum. The product was purified by chromatography on SiO2 eluting with 80% acetone:hexanes to give the titled compound. LRMS calc: 411.18; obs: 412.08 (M+1). Compounds reported in Table 7 are prepared by a general procedure analogous to that described in Example 44 above.

Provenance & Evidence