Dichloromethane → 5-amino-1-(2-bromo-6-chlorophenyl)-1H-pyrazole-4-carbonitrile

(2-Bromo-6-chlorophenyl)hydrazine hydrochloride (Intermediate AH2) (4.71 g, 18.26 mmol) was partitioned between DCM (300 mL) and 2M NaOH (20 mL). Allowed to Stir for 1 hour. The two phases were separated. The organic phase was reduced under vacuum to give the free base. This was dissolved in MeOH (60 mL), and stirred in a cooling bath at 0° C. (Ethoxymethylene)malononitrile (2.230 g, 18.26 mmol) added portionwise. The reaction mixture was then allowed to warm to ambient temperature and stirred for 1 hour. The mixture was then heated to reflux and stirred for 16 hours. Allowed to cool to ambient temperature. The reaction mixture was concentrated to give a solid, which was triturated under MeOH. A solid was filtered off. This was dried to afford the product (4.59 g, 85%). 1H NMR (400 MHz, DMSO) δ 6.79 (2H, s), 7.54-7.47 (1H, m), 7.70 (1H, dd), 7.79 (1H, s), 7.81 (1H, d). m/z (ES+) (M+H)+=299; HPLC tR=1.70 min.

1. customThe two phases were separated
2. customto give the free base
3. additionadded portionwise
4. stirringstirred for 1 hour
5. temperatureThe mixture was then heated
6. temperatureto reflux
7. stirringstirred for 16 hours
8. temperatureAllowed to cool to ambient temperature
9. concentrationThe reaction mixture was concentrated
10. customto give a solid, which
11. customwas triturated under MeOH
12. filtrationA solid was filtered off
13. customThis was dried

ORD-Eintrag

ord-862d4ba7191e48448c43559b9a778530

Quelldatensatz

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08071608B2