2-Propenoic acid, 2-cyano-3-ethoxy-, ethyl ester → ethyl 5-amino-1-(oxan-4-yl)-1H-pyrazole-4-carboxylate

HRID 12883

Reaction equation

Cl.[O:2]1[CH2:7][CH2:6][CH:5]([NH:8][NH2:9])[CH2:4][CH2:3]1.C(O[CH:13]=[C:14]([C:20]#[N:21])[C:15]([O:17][CH2:18][CH3:19])=[O:16])C.C([O-])(=O)C.[Na+]>C(O)C>[CH2:18]([O:17][C:15]([C:14]1[CH:13]=[N:9][N:8]([CH:5]2[CH2:6][CH2:7][O:2][CH2:3][CH2:4]2)[C:20]=1[NH2:21])=[O:16])[CH3:19]

Participants

Conditions

Temperature: 82.5 °C

Procedure

(Tetrahydro-pyran-4-yl)-hydrazine hydrochloride (1.975 g, 12.94 mmol), ethyl (ethoxymethylene)-cyanoacetate (1.958 g, 11.57 mmol) and sodium acetate (1.370 g; 16.70 mmol) were combined in ethanol (16 mL). The mixture was heated at 80-85° C. for 17 hours. After cooling to room temperature, the reaction was concentrated and the residue was partitioned between methylene chloride and water. The organic phase was separated and washed with water and then brine. Each aqueous phase was back extracted with methylene chloride. The two organic phases were combined, dried over sodium sulfate and concentrated in vacuo. The crude material was purified by flash chromatography eluting with 60-100% ethyl acetate/hexanes to give 5-amino-1-(tetrahydro-pyran-4-yl)-1H-pyrazole-4-carboxylic acid ethyl ester (2.554 g, 92%).

Workup

temperatureAfter cooling to room temperature
concentrationthe reaction was concentrated
customthe residue was partitioned between methylene chloride and water
customThe organic phase was separated
washwashed with water
extractionEach aqueous phase was back extracted with methylene chloride
dry with materialdried over sodium sulfate
concentrationconcentrated in vacuo
customThe crude material was purified by flash chromatography
washeluting with 60-100% ethyl acetate/hexanes

Sources & evidence

ORD record: ord-6f68aa42048a4899b155725c5423f581
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07728029B2

Linked notes

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