Pyridine → N-methyl-2-(pyridin-3-yl)thiazol-5-amine

A suspension of phosphorus pentasulfide (1.73 g, 7.8 mmol) and N-methylcarbamoylmethyl-nicotinamide (1 g, 5 mmol) in dry toluene (10 mL) was stirred at reflux under nitrogen for 16 h. The mixture was cooled to room temperature and then dry pyridine (4 mL) was added. The mixture was stirred at reflux under nitrogen for 8 h, then it was cooled to room temperature and the organic layer was removed. The dark residue was treated with hot saturated aqueous sodium bicarbonate (Na2CO3, 40 mL) and the aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed with brine (50 mL), dried over magnesium sulfate (MgSO4), and purified by silica gel chromatography (1% methanol in dichloromethane) to yield a brown amorphous solid (0.22 g, 22%): mp 141-146° C.; 1H NMR (300 MHz, CDCl3) δ 8.97 (d, J=2.4 Hz, 1H), 8.53 (dd, J=5.0, 1.8 Hz, 1H), 8.06 (ddd, J=7.2, 3.3, 0.6 Hz, 1H), 7.31 (ddd, J=5.5, 4.7, 0.5 Hz, 1H), 6.96 (s, 1H), 2.97 (d, J=5.0 Hz, 3H); ESIMS m/z 192 (M+1).

1. temperatureat reflux under nitrogen for 16 h
2. stirringThe mixture was stirred
3. temperatureat reflux under nitrogen for 8 h
4. temperatureit was cooled to room temperature
5. customthe organic layer was removed
6. additionThe dark residue was treated with hot saturated aqueous sodium bicarbonate (Na2CO3, 40 mL)
7. extractionthe aqueous layer was extracted with ethyl acetate (2×50 mL)
8. washThe combined organic extracts were washed with brine (50 mL)
9. dry with materialdried over magnesium sulfate (MgSO4)
10. custompurified by silica gel chromatography (1% methanol in dichloromethane)

ORD record

ord-ad66380b1d154df09dd685356f752713

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09006446B2