Diisopropylethylamine → 1-Oxa-2-aza-spiro[4.5]dec-2-ene-3-carboxylic acid [4-amino-5-(3-hydroxy-3-methyl-butyl)-2'-trifluoromethyl-biphenyl-3-yl]-amide

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Reaction Steps

4-(4,5-Diamino-2′-trifluoromethyl-biphenyl-3-yl)-2-methyl-butan-2-ol (57.5 mg, 0.170 mmol, as prepared in the previous step) was placed in a 50 mL round-bottom flask equipped with a magnetic stir bar. DCM (15 mL), PyBrOP (95.0 mg, 0.204 mmol), and DIPEA (36.0 μL, 0.204 mmol) were added via syringe. 1-Oxa-2-aza-spiro[4.5]dec-2-ene-3-carboxylic acid (31.0 mg, 0.170 mmol, as prepared in Example 1, step B) in DCM (10 mL) was placed in an addition funnel and added dropwise over 2 h. After completion of the addition, the mixture was stirred at rt for 2 h. The solvent was removed under reduced pressure. The residue was chromatographed on a 40-g pre-packed SiO2 column eluting with EtOAc/heptane, 0:1 to 3:7, v/v over 20 min, yielding 34.4 mg (40%) of the title compound. Mass Spectrum (LCMS, ESI pos.) Calcd. for C27H32F3N3O3: 504.2 (M+H). Found 504.1.

Provenance & Evidence