2-(Ethoxymethylene)propanedinitrile → 5-amino-1-isopropyl-1H-pyrazole-4-carbonitrile

(Ethoxymethylene)malononitrile (12.83 g, 105 mmol) and isopropylhydrazine hydrochloride (11.06 g, 100 mmol) were combined in EtOH (250 mL). Diisopropylethylamine (36.6 mL, 210 mmol) was added drop-wise, resulting in some warming of the reaction mixture. The reaction was allowed to stir for about 18 h at room temp. Volatiles were then removed in vacuo, and the resulting viscous yellow oil was dissolved in dichloromethane and loaded onto a short column of silica gel. The column was eluted with dichloromethane (about 300 mL), followed by a 1:1 mixture of EtOAc and hexanes (about 750 mL), and the EtOAc:hexanes eluant was concentrated under reduced pressure to provide C20 as a pale yellow solid. Yield: 12.1 g, 80.6 mmol, 81%. LCMS m/z 151.1 (M+1). 1H NMR (400 MHz, DMSO-d6) δ 1.26 (d, J=6.6 Hz, 6H), 4.41 (septet, J=6.5 Hz, 1H), 6.52 (br s, 2H), 7.53 (s, 1H).

1. customresulting in
2. temperaturesome warming of the reaction mixture
3. customVolatiles were then removed in vacuo
4. dissolutionthe resulting viscous yellow oil was dissolved in dichloromethane
5. washThe column was eluted with dichloromethane (about 300 mL)
6. additionfollowed by a 1:1 mixture of EtOAc and hexanes (about 750 mL)
7. concentrationthe EtOAc:hexanes eluant was concentrated under reduced pressure
8. customto provide C20 as a pale yellow solid

ORD record

ord-28750a3c66484d86be1d025aa2b5675d

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618117B2