1,2-Dichloroethane → N-[(7R)-4-Chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl]-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridine]-5-carboxamide

Participants

Reaction Steps

A mixture of (7R)-7-amino-4-chloro-9-(2,2,2-trifluoroethyl)-6,7,9,10-tetrahydroazepino[3,4-e]indazol-8(3H)-one bis-methanesulfonate from Step B (20 mg, 0.038 mmol), (±)-2′-oxo-1,1′,2′,3-tetrahydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridine]-5-carboxylic acid (11 mg, 0.038 mmol) [Bell et al. WO 2006/031606], N,N-diisopropylethylamine (25 mg, 33 uL, 0.19 mmol), HOBT (7.0 mg, 0.046 mmol), and EDC (8.8 mg, 0.046 mmol) in DMF (0.5 mL) was stirred at ambient temperature for 2 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 concentrated in vacuo to provide the title compound. MS: m/z=595.

Provenance & Evidence