1,2-Dichloroethane → N-[(7R)-4-chloro-10-(1-hydroxy-1-methylethyl)-3,6,7,12-tetrahydroimidazo[1',2':1,7]azepino[3,4-e]indazol-7-yl]-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridine]-5-carboxamide

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Reaction Steps

A solution of 2-[7-amino-4-chloro-3,6,7,12-tetrahydroimidazo[1′,2′:1,7]azepino[3,4-e]indazol-10-yl]propan-2-ol (100 mg, 0.3 mmole) and (±)-2′-oxo-1,1′,2′,3-tetrahydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridine]-5-carboxylic acid (78 mg, 0.28 mmol) [Bell et al. WO 2006/031606], HOBT (43 mg, 0.28 mmol), and EDC (54 mg, 0.28 mmol) in DMF (2 mL) was stirred at ambient temperature for 1 h. The reaction mixture was purified directly by HPLC using a reversed phase C18 column and eluting with a gradient of H2O:CH3CN:CF3CO2H-90:10:0.1 to 5:95:0.1. The pure, product-containing fractions were combined and made basic with saturated aqueous NaHCO3. The resulting mixture was extracted with EtOAc (2×20 mL), and the combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to provide the title compound as an off white solid. MS: m/z=594 (M+1)

Provenance & Evidence