2-Propenoic acid, 2-cyano-3-ethoxy-, ethyl ester → ethyl 5-amino-1-cyclopentyl-1H-pyrazole-4-carboxylate

HRID 12886

Reaction equation

Cl.[CH:2]1([NH:7][NH2:8])[CH2:6][CH2:5][CH2:4][CH2:3]1.C(O[CH:12]=[C:13]([C:19]#[N:20])[C:14]([O:16][CH2:17][CH3:18])=[O:15])C.C([O-])(=O)C.[Na+]>C(O)C>[CH2:17]([O:16][C:14]([C:13]1[CH:12]=[N:8][N:7]([CH:2]2[CH2:6][CH2:5][CH2:4][CH2:3]2)[C:19]=1[NH2:20])=[O:15])[CH3:18]

Participants

Conditions

Temperature: 70 °C

Procedure

Cyclopentyl-hydrazine hydrochloride (1.000 g; 7.32 mmol), ethyl (ethoxymethylene)-cyanoacetate (1.026 g, 6.61 mmol) and anhydrous sodium acetate (0.644 g, 7.85 mmol) were combined in ethanol (10 mL) and heated at 70° C. for 20 hours. After cooling to room temperature, ethanol was removed in vacuo and the residue was partitioned between methylene chloride and water. The organic phase was washed sequentially with water and brine. Each aqueous phase was back extracted with a single portion of methylene chloride. The two organic phases were combined, dried over sodium sulfate and concentrated. Purification by flash chromatography, eluting with 10-40% EtOAc/hexanes yielded 5-amino-1-cyclopentyl-1H-pyrazole-4-carboxylic acid ethyl ester (1.170 g, 73%). Mass spectrum: m/z: 224.1 (M+H).

Workup

temperatureAfter cooling to room temperature
customethanol was removed in vacuo
customthe residue was partitioned between methylene chloride and water
washThe organic phase was washed sequentially with water and brine
extractionEach aqueous phase was back extracted with a single portion of methylene chloride
dry with materialdried over sodium sulfate
concentrationconcentrated
customPurification by flash chromatography
washeluting with 10-40% EtOAc/hexanes

Sources & evidence

ORD record: ord-660058880d6144ccbdfae5625f97875b
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07728029B2

Linked notes

Loading…