N-[(4-methoxyphenyl)methyl]-1,3-thiazol-2-amine → HCID 86687562, compound

Temperature

-78 °C

A round-bottom flask was charged with N-(4-methoxybenzyl)thiazol-2-amine (0.048 g, 0.218 mmol) and THF (1.00 mL), and the vessel was cooled to −78° C. for 15 minutes. LHMDS (1.0 M in THF) (0.238 ml, 0.238 mmol) was then added drop wise over 1 minute. The reaction was stirred for 10 minutes, and then a solution of 4-(2-methoxy-4-(trifluoromethyl)phenyl)-1,6-naphthyridine-7-sulfonyl chloride (0.080 g, 0.199 mmol) in THF (1.00 mL) was added drop wise. The bath was removed, and the resulting mixture was stirred for 45 minutes. The reaction was diluted with saturated ammonium chloride (aq.) solution (30 mL), and was washed with ethyl acetate (20 mL×3). The organic layers were combined, dried over magnesium sulfate, filtered and concentrated. The resulting material was purified via silica gel MPLC chromatography (40 g), eluting with 0 to 100% ethyl acetate in heptanes. The fractions were concentrated under reduced pressure and the resulting material was taken up in DCM (10 mL) and TFA (1 mL) was added. The reaction was stirred for 2 hours and then the solvent was removed under reduced pressure. The resulting material was taken up in DCM (30 mL) and washed with aqueous sodium bicarbonate (sat. solution). The organic layer was dried over magnesium sulfate, filtered and concentrated. The resulting solid was triturated with diethyl ether (20 mL) and filtered. The solid was dried under reduced pressure to provide 0.018 g of 4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-1,6-naphthyridine-7-sulfonamide as an off white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.86 (s, 3H) 6.94 (d, J=4.60 Hz, 1H) 7.34 (d, J=4.60 Hz, 1H) 7.56-7.62 (m, 2H) 7.69 (d, J=7.73 Hz, 1H) 7.81 (d, J=4.50 Hz, 1H) 8.47-8.51 (m, 1H) 8.98-9.02 (m, 1H) 9.36 (d, J=4.50 Hz, 1H) 12.99 (br. s., 1H). m/z (ESI) 467.1 (M+H)+.

1. customThe bath was removed
2. stirringthe resulting mixture was stirred for 45 minutes
3. additionThe reaction was diluted with saturated ammonium chloride (aq.) solution (30 mL)
4. washwas washed with ethyl acetate (20 mL×3)
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customThe resulting material was purified via silica gel MPLC chromatography (40 g)
9. washeluting with 0 to 100% ethyl acetate in heptanes
10. concentrationThe fractions were concentrated under reduced pressure
11. additionTFA (1 mL) was added
12. stirringThe reaction was stirred for 2 hours
13. customthe solvent was removed under reduced pressure
14. washwashed with aqueous sodium bicarbonate (sat. solution)
15. dry with materialThe organic layer was dried over magnesium sulfate
16. filtrationfiltered
17. concentrationconcentrated
18. customThe resulting solid was triturated with diethyl ether (20 mL)
19. filtrationfiltered
20. customThe solid was dried under reduced pressure

ORD record

ord-fde3afce155b4bf7877ed305dff4a3ce

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09012443B2