2,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo(3.3.3)undecane → Hydrochloric Acid

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-chloro-6-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-5-methoxy-pyrimidine (1.78 g, 5.03 mmol), 6-Methanesulfonyl-2-methyl-pyridin-3-ylamine (1.12 g, 6.04 mmol), palladium acetate (102 mg, 0.45 mmol), 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phospha-bicyclo[3.3.3]undecane (322 μl, 0.91 mmol) and sodium tert-butoxide (725 mg, 7.54 mmol) in 30 mL of dioxane was heated under microwave irradiation at 150° C. for 1 hr. Additional 40 mL of dioxane were added and the mixture was refluxed under 130° C. After 65 hr, mixture was purified by HPLC. Fractions with product were collected, concentrated, and recrystalized with hot ethanol. 4N HCl in dioxane (ca 1 mL) and acetonitrile (ca 3 mL) were added and concentrated to give {6-[1-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yloxy]-5-methoxy-pyrimidin-4-yl}-(6-methanesulfonyl-2-methyl-pyridin-3-yl)-amine as white solid (HCl salt, 360 mg, 13.3%). 1HNMR (DMSO-d6, 400 MHz) δ 1.19-1.21 (d, J=6.82 Hz, 6H), 1.83-1.85 (m, 2H), 2.06-2.08 (m, 2H), 2.51 (s, 3H), 2.81-2.84 (sept, J=6.82 Hz, 1H), 3.57-3.59 (m, 2H), 3.75-3.77 (m, 2H), 3.87 (s, 1H), 5.31-3.39 (m, 1H), 7.89-7.91 (d, J=8.34 Hz, 1H), 8.07 (s, 1H), 8.23-8.25 (d, J=8.34 Hz, 1H) 8.69 (s, 1H). Exact mass calculated for C22H29N7O5S 503.2 found 504.2 (MH+).

Provenance & Evidence