Water → N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-((6-fluoro-1H-pyrrolo[3,2-b]pyridin-5-yl)methyl)-N2-methylpyrimidine-2,4-diamine

온도

63 °C

A mixture of N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-((6-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[3,2-b]pyridin-5-yl)methyl)-N2-methylpyrimidine-2,4-diamine (40 mg, 0.1 mmol) and tetrabutyl ammonium fluoride (260 mg, 1 mmol) in THF (5 mL) was heated at 63° C. for 18 h. The reaction mixture was poured into water (10 mL) and the pH was adjusted to 10 by addition of an NH4OH solution. The mixture was extracted with EtOAc (50 mL×3) and the combined extracts dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was purified by reverse phase preparative HPLC to afford 8 mg, (20%) of N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-((6-fluoro-1H-pyrrolo[3,2-b]pyridin-5-yl)methyl)-N2-methylpyrimidine-2,4-diamine as a white solid. 1H NMR (500 MHz, DMSO) δ 11.8 (brs, 1H), 11.3 (brs, 1H), 9.33 (brs, 1H), 7.85 (d, J=5 Hz, 1H), 7.65 (d, 0.1=10 Hz, 1H), 7.58 (d, J=3 Hz, 1H), 6.51 (s, 1H), 6.00-6.20 (brs, 2H), 5.06 (s, 2H), 3.16 (s, 3H), 1.81 (s, 1H), 0.85 (s, 2H), 0.59 (s, 2H); MS (ESI): m/z=379.3 [M+1]+.

1. extractionThe mixture was extracted with EtOAc (50 mL×3)
2. dry with materialthe combined extracts dried (MgSO4)
3. filtrationfiltered
4. concentrationconcentrated under reduced pressure
5. customThe residue was purified by reverse phase preparative HPLC

ORD 기록

ord-42b5918875d84f5a93559af08fd8821d

출처 데이터셋

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08815877B2