Potassium Phosphate, Tribasic → 3-(4-{[(1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl]methoxy}-2-methylpyrimidin-5-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole

温度

100 °C

A mixture of 5-bromo-4-{[(1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl]-methoxy}-2-methylpyrimidine (2-3) (120 mg, 0.3 mmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole (OO2) (104 mg, 0.4 mmol), tripotassium phosphate (145 mg, 0.7 mmol), S-Phos (14 mg, 0.03 mmol), and Pd(OAc)2 (3.9 mg, 0.02 mmol) in THF (1.5 mL) and water (0.3 mL) was heated at 100° C. for 14 hours. The reaction mixture was allowed to cool to room temperature. The mixture was then diluted with EtOAc (10 mL), washed with sodium bicarbonate (2 mL) and brine (2 mL), dried over MgSO4, filtered and concentrated. The crude residue was purified by reverse phase chromatography (Waters Sunfire Prep C18 OBD, 5-45% acetonitrile in water with 0.1% TFA modifier) to afford the title compound as a colorless gum. 1H NMR (500 MHz, DMSO): δ 8.51 (s, 1 H), 8.14 (d, J=2.9 Hz, 1 H), 7.84 (s, 1 H), 7.31-7.22 (m, 2 H), 4.53 (dd, J=11.3, 6.4 Hz, 1 H), 4.25 (dd, J=11.3, 8.2 Hz, 1 H), 4.04 (t, J=7.3 Hz, 2 H), 3.78 (s, 3 H), 2.97 (t, J=7.3 Hz, 2 H), 2.50 (s, 3 H), 2.39-2.32 (m, 2 H), 2.19 (dd, J=8.4, 4.7 Hz, 1 H), 1.79 (m, 1 H), 1.17 (dt, J=8.6, 4.5 Hz, 1 H), 1.06 (dd, J=8.6, 4.9 Hz, 1 H); HRMS m/z (M+H) 378.1921 found, 378.1925 required.

1. temperatureto cool to room temperature
2. washwashed with sodium bicarbonate (2 mL) and brine (2 mL)
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated
6. customThe crude residue was purified by reverse phase chromatography (Waters Sunfire Prep C18 OBD, 5-45% acetonitrile in water with 0.1% TFA modifier)

ORDレコード

ord-3cc8ecd0997f4e5182910b276a20fb00

出典データセット

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08975261B2