1,2-Dichloroethane → HCID 178504214, compound

Participants

Reaction Steps

{3-[4-(7-{[2-(Trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile dihydrochloride (1.20 g, 2.49 mmol) (from WO 2009114512) and 4-{[6-(hydroxymethyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexanone (0.900 g, 3.10 mmol) in dry 1,2-dichloroethane (30.00 mL, 380.8 mmol) were stirred for 5 minutes, and sodium triacetoxyborohydride (1.87 g, 8.82 mmol) was added. The reaction mixture was stirred at room temperature for 16 hours, at which time LCMS analysis showed mainly the two diastereomeric products. The reaction was quenched with water, neutralized with NaHCO3 and extracted with ethyl acetate. The mixture was purified by preparative-HPLC/MS (C18 column eluting with a gradient of ACN/H2O containing 0.15% NH4OH). Fractions containing the second peak were combined and stripped down to give {1-(cis-4-{[6-(hydroxymethyl)-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. 1H NMR (500 MHz, CDCl3) δ: 8.90 (s, 1H), 8.47 (s, 1H), 8.37 (s, 1H), 7.46 (d, 1H), 6.98 (s, 1H), 6.86 (d, 1H), 5.73 (s, 2H), 5.41 (m, 1H), 4.80 (s, 2H), 3.82 (d, 2H), 3.67 (d, 2H) 3.59 (m, 2H), 3.46 (s, 2H), 3.15 (m, 1H), 2.42 (m, 2H), 2.11 (m, 2H), 1.70-1.90 (m, 6H), 0.96 (m, 2H), −0.4 (s, 9H). MS (ES): 683 (M+1).

Provenance & Evidence