Acetic Acid → Ammonium Hydroxide

Participants

Reaction Steps

To a solution of (7S)-3-{[(2R)-2-(3,5-difluorophenyl)-2,5,5-trimethyl-6-oxopiperazin-1-yl]methyl}-6,8-dihydrospiro[cyclopenta[g]quinoline-7,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one, isomer B (15 mg, 0.027 mmol, described in Example 18), paraformaldehyde (8.1 mg, 0.27 mmol), and AcOH (0.0078 mL, 0.14 mmol) in MeOH (1 mL) was added NaCNBH3 (2.0 mg, 0.033 mmol). The reaction mixture was stirred for 16 h and then diluted with saturated aqueous NaHCO3 (10 mL) and extracted with CH2Cl2 (3×10 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was dissolved in MeOH (1 mL). Sodium hydroxide (10 M, 0.014 mL, 0.14 mmol) and ethylenediamine (0.0037 mL, 0.054 mmol) were added and the solution was stirred for 30 min and then diluted with saturated aqueous NaHCO3 (5 mL) and extracted with CH2Cl2 (3×5 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH:NH4OH—100:0:0 to 90:10:1, to give the title compound. MS: m/z=568 (M+1). HRMS: m/z=568.2520; calculated m/z=568.2519 for C33H32F2N5O2.

Provenance & Evidence