تفاعل #2033239

معادلة التفاعل

2-chloro-8-[2-(4,4-difluoropiperidin-1-yl)ethyl]-9-methyl-6-morpholin-4-yl-9H-purine

2-ethylbenzimidazole

Xphos

Cs2CO3

→

540

المردود 64.0%

4-(8-(2-(4,4-difluoropiperidin-1-yl)ethyl)-2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-9H-purin-6-yl)morpholine

المردود 64.0%

المذيبات

dioxane

ظروف التفاعل

المعالجة

1. 1
   أخرىwas purged with argon gas
2. 2
   غسيلwashed with MeOH
3. 3
   غسيلthe desired product eluted with 2 M NH3/MeOH in DCM
4. 4
   أخرىThe resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 20 mM triethylamine in water on a gradient of acetonitrile 30-90%)

الإجراء التجريبي

A mixture of 2-chloro-8-[2-(4,4-difluoropiperidin-1-yl)ethyl]-9-methyl-6-morpholin-4-yl-9H-purine (30 mg, 0.08 mmol), 2-ethylbenzimidazole (12 mg, 0.08 mmol), Pd2(dba)3 (1.7 mg, 2.5 mol %), Xphos (3.6 mg, 10 mol %) and Cs2CO3 (37 mg, 0.11 mmol) in dioxane (1.0 mL) was purged with argon gas then heated at 120° C., for 20 h, in a sealed tube. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge, washed with MeOH then the desired product eluted with 2 M NH3/MeOH in DCM. The resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 20 mM triethylamine in water on a gradient of acetonitrile 30-90%) to give 540 (25 mg, 64%) as a beige solid. LCMS: (Method I): RT 2.61 min; [M+H]+ 511.2. 1H NMR (400 MHz, CHCl3-d): δ 8.01-7.96 (m, 1 H), 7.78-7.74 (m, 1 H), 7.29-7.23 (m, 2 H), 4.68-4.02 (m, 4 H), 3.86 (t, J=4.8 Hz, 4 H), 3.78 (s, 3 H), 3.35 (q, J=7.5 Hz, 2 H), 3.12-2.99 (m, 4 H), 2.81-2.65 (m, 4 H), 2.15-1.99 (m, 4 H), 1.44 (t, J=7.5 Hz, 3 H)

المصدر