反应详情

To a 2 mL microwave vial were added 6-bromo-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide (150 mg, 0.338 mmol), 2-(4-methyl-1-piperazinyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine (134 mg, 0.440 mmol), Na2CO3 (108 mg, 1.015 mmol), PdCl2(dppf)-CH2Cl2 adduct (27.6 mg, 0.034 mmol), 1,2-Dimethoxyethane (1269 μl) and water (423 μl). The contents were irradiated in a microwave reactor at 150° C. for 30 min. The reaction solution was filtered through a Whatman 0.45 μl Teflon syringless filter device and diluted with DMSO (6 mL). The DMSO solution was purified by HPLC reverse phase chromatography (phenomenex Gemini-NX, 30×100 5μ column, 5-30% acetonitrile/water 0.01% formic acid, 8 min gradient). The fractions containing the desired product were concentrated to dryness using a Genovac HT-4 instrument at 40° C. The title compound was obtained as a pale cream colored foam (28 mg, 14.83% yield). 1H NMR (400 MHz, CHLOROFORM-6) δ 8.62 (s, 2H), 8.39 (s, 1H), 7.99 (t, J=5.56 Hz, 1H), 7.71 (s, 1H), 7.57 (s, 1H), 5.98 (s, 1H), 5.03 (quin, J=7.14 Hz, 1H), 4.66 (d, J=5.81 Hz, 2H), 3.97 (br. s., 4H), 2.64 (br. s., 4H), 2.44 (s, 6H), 2.12-2.25 (m, 7H), 1.89-2.07 (m, 2H), 1.67-1.85 (m, 2H). LCMS (ES) [M+H]+ 541.5.

1. customThe contents were irradiated in a microwave reactor at 150° C. for 30 min
2. filtrationThe reaction solution was filtered through a Whatman 0.45 μl Teflon syringless filter device
3. additiondiluted with DMSO (6 mL)
4. customThe DMSO solution was purified by HPLC reverse phase chromatography (phenomenex Gemini-NX, 30×100 5μ column, 5-30% acetonitrile/water 0.01% formic acid, 8 min gradient)
5. additionThe fractions containing the desired product
6. concentrationwere concentrated to dryness
7. customat 40° C