HCID 15020539, compound → HCID 14823467, compound

Participants

Reaction Steps

To a stirred solution of 4-(5-chloro-1H-indazol-3-yl)-1-piperazinecarbonitrile of Example 36a in THF (175 ml) under N2 was added, dropwise, lithium aluminum hydride (20 ml, 0.02 mol of a 1M lithium aluminum hydride solution in THF). After total addition, the reaction was heated to reflux and stirred for 3 hours. The reaction was cooled in an ice bath and the excess lithium aluminum hydride was destroyed by the dropwise addition of H2O (15 ml). This was filtered through a coarse sintered glass funnel and the filter cake was washed well with THF. The filtrate was concentrated to afford a biphasic H2O-oil (7.5 g). This was partitioned between CH2Cl2 and H2O and the H2O was extracted again with CH2Cl2 adding a small amount of saturated NaCl solution. The combined CH2Cl2 extract was washed with H2O, dried with MgSO4 and concentrated to afford 3.2 g of a solid, m.p. 60°-62° C. The solid was purified by preparative HPLC (Water's Associates Prep. LC/System 500, 2 silica gel columns eluting with 20% methanol-CH2Cl2) to afford 1.9 g of product. A small amount was recrystallized from toluene and collected, then washed with hexane affording solid 5-chloro-3-(1-piperazinyl)-1H-indazole, m.p. 178°-180° C.

Provenance & Evidence