2,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo(3.3.3)undecane → HCID 11648576, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-(6-chloro-5-methoxy-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester (0.966 g, 2.93 mmol), 2-methyl-6-propylsulfanyl-pyridin-3-ylamine (0.545 g, 2.99 mmol), palladium acetate (0.0375 g, 0.167 mmol), 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phospha-bicyclo[3.3.3]undecane (0.119 mL, 0.335 mmol), and sodium 2-methylpropan-2-olate (0.422 g, 4.39 mmol) in 15 mL dioxane was heated under microwave irradiation at 120° C. After 2 h, mixture was purified by HPLC; fractions containing pure product were collected, partly concentrated, and residue was extracted with CH2Cl2 and 1M NaOH. Organic phases were dried over MgSO4, filtered, and concentrated to give 4-[5-methoxy-6-(2-methyl-6-propylsulfanyl-pyridin-3-ylamino)-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester as a thick oil (0.509 g, 36%). 1HNMR (MeOH-d4, 400 MHz) δ 1.00-1.04 (t, J=7.3 Hz, 3H), 1.23-1.24 (d, J=6.2 Hz, 6H), 1.66-1.78 (m, 4H), 1.96-2.02 (m, 2H), 2.37 (s, 3H), 3.06-3.10 (t, J=7.3 Hz, 2H), 3.36-3.42 (m, 2H), 3.71-3.77 (m, 2H), 3.88 (s, 3H), 4.81-4.87 (m, 1H), 5.28-5.34 (m, 1H), 7.09-7.11 (d, J=8.3 Hz, 1H), 7.57-7.59 (d, J=8.3 Hz, 1H), 7.84 (s, 1H). Exact mass calculated for C23H33N5O4S 475.23 found 476.1 (MH+).

Provenance & Evidence