Water → HCID 178458734, compound

Participants

Reaction Steps

Methylene chloride (2.0 mL) and trifluoroacetic acid (0.40 mL, 5.2 mmol) were added to {1-(cis-4-{[6-(1-hydroxy-1-methylethyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile, stirred for 2 hours, and then concentrated to remove trifluoroacetic acids. LCMS showed clean conversion to the hydroxymethyl intermediate (M+2H 320). To the residue was added methanol (2.0 mL), then 15.0 M ammonium hydroxide in water (1.8 mL, 27 mmol). The solution was stirred 2.5 hours. LCMS showed the reaction was complete. The product was isolated by preparative LCMS using a Waters Fraction-Linx instrument and a 30 mm×100 mm Sunfire C18 column (5% CH3CN—H2O (0.1% TFA), 4.0 minutes; 8.0 min gradient to 30%; 60 mL/min; 8 runs; retention time 11.0 minutes). The eluent was concentrated by 50%, then freeze-dried to give white solid. 1H NMR (300 MHz, MeOH-D4): δ 8.99 (s, 1H); 8.82 (s, 1H); 8.57 (s, 1H); 7.71 (m, 1H); 7.20 (s, 1H); 7.16 (m, 1H); 5.48 (m, 1H, OCH); 5.06 (d, 2H azetidine) 4.8 (d, 2H, azetidine); 3.70 (s, 2H, CH2CN); 3.50 (m, 1H, NCH); 2.30 (m, 2H); 2.01 (m, 2H); 1.80 (m, 2H); 1.75 (m, 2H); 1.50 (s, 6H). MS: 582 (M+H)

Provenance & Evidence