Potassium Carbonate → (1R,2R)-2-((6-((6-cyclopropyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol

温度

100 °C

A stirred mixture of (1R,2R)-2-((6-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol from Example 29 (30 mg, 0.0656 mmol), cyclopropylboronic acid (11 mg, 0.131 mmol), K2CO3 (36 mg, 0.262 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (16 mg, 0.0328 mmol) and anhydrous toluene (1 mL) was degassed under argon for 15 min. Tris(dibenzylideneacetone)dipalladium (0) (6 mg, 0.0066 mmol) was added. The reaction vessel was sealed and the mixture was heated at 100° C. for 15 h. After cooling to rt, the mixture was purified directly by reverse-phase HPLC using a mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Phenomenex Luna C-18 column as the stationary phase to afford (1R,2R)-2-((6-((6-cyclopropyl-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (1 mg, 4%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.51 (s, 1H), 8.24 (d, J=1.5 Hz, 1H), 8.03 (d, J=7.3 Hz, 1H), 7.70 (d, J=1.5 Hz, 1H), 7.63 (s, 1H), 7.28 (m, 1H), 7.19 (m, 1H), 5.44 (s, 2H), 4.82 (br s, 1H), 1.97-2.13 (m, 2H), 1.85 (m, 1H), 1.54-1.74 (m, 3H), 1.09-1.34 (m, 4H), 0.92-1.02 (m, 2H), 0.70-0.80 (m, 2H). LCMS (ESI) m/z 420 (M+H)+.

1. customwas degassed under argon for 15 min
2. customThe reaction vessel was sealed
3. temperatureAfter cooling to rt
4. customthe mixture was purified directly by reverse-phase
5. additiona mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Phenomenex Luna C-18 column as the stationary phase

ORDレコード

ord-965192c0ad6e48d782f3496cb4b78017

出典データセット

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08952058B2