Sodium Carbonate → HCID 131735894, compound

Participants

Reaction Conditions

Reaction Steps

2-Methyl-THF (1.48 mL), sodium carbonate (2M, 223 μL, 0.446 mmol) and 2-(5-bromopyridin-2-yl)-1-{[tert-butyl(dimethyl)silyl]oxy}propan-2-ol (170 mg, 0.490 mmol) were added to N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (169 mg, 0.446 mmol) and purged and flushed with Ar(g) (3×). PdCl2(dppf)-dichloromethane adduct (18.2 mg, 0.022 mmol) was added to the reaction mixture, purged and flushed with Ar(g) (3×) and heated to 85° C. for 2 hours. The reaction was cooled to room temperature and was diluted with water (5.00 mL), extracted with DCM (5.00 mL), dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (acetone/hexanes) to yield 1-{[tert-butyl(dimethyl)silyl]oxy}-2-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]propan-2-ol. The isolated intermediate was dissolved in neat TFA (1.00 mL) and stirring for 20 minutes at room temperature. The excess TFA was removed under reduced pressure and the resultant residue was partitioned with dichloromethane (5.00 mL) and 1M NaOH (aq) (5.00 mL). The organic layer was washed with brine (5.00 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (acetone/hexanes) to yield 2-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]propane-1,2-diol. MS APCI calc'd for C20H20F3N4O2 [M+H]+ 405. found 405. 1H NMR (500 MHz, DMSO-d6) δ 10.27 (s, 1H), 8.83 (d, J=5.5 Hz, 1H), 8.72 (s, 1H), 7.96 (d, J=16.2 Hz, 1H), 7.70 (d, J=9.2 Hz, 1H), 7.55 (s, 1H), 7.27 (d, J=5.5 Hz, 1H), 7.18 (s, 1H), 5.13 (s, 1H), 4.64 (s, 1H), 3.57 (d, J=7.6 Hz, 2H), 2.36 (s, 3H), 1.40 (s, 3H).

Provenance & Evidence