Carbon tetrabromide → HCID 58671559, compound

Participants

Reaction Steps

To an ice-cooled solution of 4-{6-[6-(2-hydroxy-ethyl)-2-methyl-pyridin-3-ylamino]-5-methoxy-pyrimidin-4-yloxy}-piperidine-1-carboxylic acid isopropyl ester (40.2 mg, 90.2 μmol) and triphenylphosphine (31 mg, 118 pmol) in 2 mL methylene chloride, perbromomethane (77.0 mg, 232 μmol) were added and solution was stirred at room temperature. After 18 h, the mixture was concentrated, re-dissolved in 1.5 mL MeOH, and added to a well stirred mixture of sodium hydroxide (120 mg, 3.0 mmol) and 2-methyl-2-thiopseudourea sulfate (208 mg, 0.70 mmol) in 2 mL MeOH. After stirring at room temperature for 17 h, mixture was concentrated and extracted with water and methylene chloride. Organic phases were concentrated and purified by HPLC to give 4-{5-methoxy-6-[2-methyl-6-(2-methylsulfanyl-ethyl)-pyrdin-3-ylamino]-pyrimidin-4-yloxy}-piperidine-1-carboxylic acid isopropyl ester (TFA salt, 10.0 mg, 19%) as a white solid. 1HNMR (MeOH-d4, 400 MHz) δ 1.21-1.23 (d, J=6.2 Hz, 6H), 1.72-1.78 (m, 2H), 1.94-2.01 (m, 2H), 2.12 (s, 3H), 2.65 (s, 3H), 2.90-2.93 (t, J=7.2 Hz, 2H), 3.24-3.27 (t, J=7.2 Hz, 2H), 3.39-3.46 (m, 2H), 3.69-3.76 (m, 2H), 3.91 (s, 3H), 4.80-4.86 (m, 2H), 5.32-5.38 (m, 1H), 7.75-7.77 (d, J=8.6 Hz, 1H), 7.96 (s, 1H), 8.57-5.59 (d, J=8.6 Hz, 1H). Exact mass calculated for C23H33N5O4S 475.23 found 476.2 (MH+).

Provenance & Evidence