3-Pyridinemethanamine → HCID 57919924, compound

A mixture of 2-(3-((2,2-difluorocyclopropyl)methyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid (0.11 g, 0.36 mmol), 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (0.23 g, 0.73 mmol), N-hydroxybenzotriazole (0.20 g, 0.15 mmol) and N,N-diisopropylethylamine (0.09 g, 0.73 mmol) in anhydrous tetrahydrofuran (3.0 mL) was stirred at ambient temperature for 15 min, followed by the addition of 3-(aminomethyl)pyridine (0.08 g, 0.73 mmol) in anhydrous tetrahydrofuran (1.0 mL). The reaction mixture was stirred at ambient temperature for 16 h, followed by the addition of saturated sodium bicarbonate solution (2 mL). The mixture was extracted with ethyl acetate (3×3 mL). The combined organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The solid was purified by flash chromatography eluted with dichloromethane in methanol (2%) to afford the title compound as a colourless solid (0.12 g, 81%): mp 169-171° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.52 (t, J=5.9 Hz, 1H), 8.49 (s, 1H), 8.42 (d, J=3.7 Hz, 1H), 7.67 (d, J=7.8 Hz, 1H), 7.32 (dd, J=7.8, 4.9 Hz, 1H), 4.35 (d, J=5.9 Hz, 2H), 3.99 (d, J=8.3 Hz, 1H), 3.61-3.47 (m, 3H), 3.20-3.12 (m, 1H), 2.44 (s, 3H), 2.05-1.88 (m, 1H), 1.67-1.55 (m, 1H), 1.37-1.27 (m, 1H); MS (ES+) m/z 409.0 (M+1).

1. stirringThe reaction mixture was stirred at ambient temperature for 16 h
2. extractionThe mixture was extracted with ethyl acetate (3×3 mL)
3. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
4. filtrationfiltered
5. concentrationThe filtrate was concentrated in vacuo to dryness
6. customThe solid was purified by flash chromatography
7. washeluted with dichloromethane in methanol (2%)

ORD record

ord-48e813a6bca148b5849d9f591914c20a

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08318949B2