3-Pyridinemethanamine → 4-methyl-2-(2-oxo-3-(pyridin-4-ylmethyl)imidazolidin-1-yl)-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide

To a solution of 4-methyl-2-(2-oxo-3-(pyridin-4-ylmethyl)imidazolidin-1-yl)thiazole-5-carboxylic acid (0.67 g, 2.12 mmol) in anhydrous N,N-dimethyl formamide (10 mL) was added benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (0.94 g, 2.12 mmol), diisopropylethylamine (1.12 mL, 6.35 mmol) and 3-(aminomethyl)pyridine (0.22 mL, 2.12 mmol). The resulting solution was stirred at ambient temperature for 24 hours. The reaction mixture was concentrated in vacuo. The residue was dissolved in dichloromethane (50 mL), washed with saturated aqueous sodium bicarbonate solution (15 mL) and brine (15 mL). The separated organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluted with 10-20% methanol in ethyl acetate as an eluent to afford the title compound as a colorless solid (10%, 0.092 g): mp 233-235° C. (dichloromethane/hexanes): 1H NMR (300 MHz, CDCl3) δ 8.57-8.49 (m, 4H), 7.67 (d, J=7.7 Hz, 1H), 7.26-7.17 (m, 3H), 6.36 (br s, 1H), 4.56 (d, J=5.8 Hz, 2H), 4.45 (s, 2H), 4.12-4.07 (m, 2H), 3.50-3.45 (m, 2H), 2.58 (s, 3H): MS (ES+) m/z 409.2 (M+1).

1. concentrationThe reaction mixture was concentrated in vacuo
2. dissolutionThe residue was dissolved in dichloromethane (50 mL)
3. washwashed with saturated aqueous sodium bicarbonate solution (15 mL) and brine (15 mL)
4. dry with materialThe separated organic layer was dried over anhydrous sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified by column chromatography
8. washeluted with 10-20% methanol in ethyl acetate as an eluent

ORD record

ord-196a88c11eb34376a177da3ec43510c6

Source dataset

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08063084B2