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

HRID 1098201Notes

Reaction equation

Cl.[CH3:2][C:3]1[CH:8]=[CH:7][C:6]([CH3:9])=[CH:5][C:4]=1[NH:10][NH2:11].C(O[CH:15]=[C:16]([C:19]#[N:20])[C:17]#[N:18])C>CO>[NH2:20][C:19]1[N:10]([C:4]2[CH:5]=[C:6]([CH3:9])[CH:7]=[CH:8][C:3]=2[CH3:2])[N:11]=[CH:15][C:16]=1[C:17]#[N:18]

Participants

Conditions

Temperature: 0 °C

Procedure

2,5-Dimethylphenylhydrazine hydrochloride (CAS no. 56737-78-1) (10 g, 57.92 mmol) was partitioned between EtOAc (100 mL) and NaOH (2M, aq) (60 mL). The organic layer separated and washed with water (50 mL), brine (50 mL), dried (MgSO4), filtered and concentrated to afford free base of the starting material. The resultant oil was suspended in MeOH (100 mL) under nitrogen at −5° C. 2-(ethoxymethylene)malononitrile (7.07 g, 57.92 mmol) added portionwise over 5 mins and the mixture stirred at ˜0° C. for 30 mins. The reaction mixture was allowed to warm to room temperature and then heated at reflux under nitrogen for 2 hours. The reaction mixture was allowed to cool and evaporated to dryness to afford the product (11.07 g, 90%) which was used without purification. 1H NMR (400 MHz, DMSO) δ 1.98 (3H, s), 2.31 (3H, s), 6.39 (2H, s), 7.07 (1H, s), 7.21-7.28 (2H, m), 7.72 (1H, s); m/z (ES+) (M+H)+=213; HPLC tR=1.79 min.

Workup

custom56737-78-1) (10 g, 57.92 mmol) was partitioned between EtOAc (100 mL) and NaOH (2M, aq) (60 mL)
customThe organic layer separated
washwashed with water (50 mL), brine (50 mL)
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated
customto afford free base of the starting material
temperatureto warm to room temperature
temperatureheated
temperatureat reflux under nitrogen for 2 hours
temperatureto cool
customevaporated to dryness

Sources & evidence

ORD record: ord-5058b66426454d478428aae33b488dd6
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08143263B2

Reaction notes

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