Ammonia → 1-(3,5-difluoro-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)thiourea

Step R (3): Dichloromethane (50 mL) was added to a flask charged with 3,5-difluoro-4-(3-methyl-1H-1,2,4-triazol-1-yl)aniline (1.75 g, 8.33 mmol) and 1,1′-thiocarbonyldipyridin-2(1H)-one (2.90 g, 8.33 mmol). The resulting mixture was stirred for 24 h at rt and concentrated in vacuo. A solution of ammonia (2.0 M in methanol, 50 mL, 100 mmol) was added to the crude solid. The heterogeneous mixture was stirred at rt for 2 h, then evaporated to dryness under reduced pressure using a rotary evaporator. The solid residue was triturated with 40 mL of anhydrous ethanol and chilled to 0° C. for 1 h. The solid was collected by vacuum filtration and dried under high vacuum to afford 1-(3,5-difluoro-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)thiourea (1.76 g, 6.54 mmol, 79% yield) as a gray powdery solid. LC-MS (M+H)+ 270.0. 1H NMR (500 MHz, DMSO-d6) d ppm 10.16 (1 H, br. s.), 8.77 (1 H, s), 7.64 (2 H, d, J=10.4 Hz), 2.35 (3 H, s).

1. concentrationconcentrated in vacuo
2. stirringThe heterogeneous mixture was stirred at rt for 2 h
3. customevaporated to dryness under reduced pressure
4. customa rotary evaporator
5. customThe solid residue was triturated with 40 mL of anhydrous ethanol
6. temperaturechilled to 0° C. for 1 h
7. filtrationThe solid was collected by vacuum filtration
8. customdried under high vacuum

ORD record

ord-42441139170d4daf9b8482a48eb0358c

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08349880B2